2-218662989-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 1P and 17B. PP3BP6_Very_StrongBP7BA1

The NM_001079866.2(BCS1L):c.996C>T(p.Asn332Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,613,760 control chromosomes in the GnomAD database, including 1,640 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 330 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1310 hom. )

Consequence

BCS1L
NM_001079866.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.15

Publications

10 publications found

Variant links:

Genes affected

BCS1L (HGNC:1020): (BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone) This gene encodes a homolog of the S. cerevisiae bcs1 protein which is involved in the assembly of complex III of the mitochondrial respiratory chain. The encoded protein does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. Mutations in this gene are associated with mitochondrial complex III deficiency and the GRACILE syndrome. Several alternatively spliced transcripts encoding two different isoforms have been described. [provided by RefSeq, Jan 2016]

BCS1L Gene-Disease associations (from GenCC):

Bjornstad syndrome
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Ambry Genetics, ClinGen, G2P
GRACILE syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
Leigh syndrome
Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, ClinGen
mitochondrial complex III deficiency nuclear type 1
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
mitochondrial complex III deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
renal tubulopathy-encephalopathy-liver failure syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BCS1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

PP3

REVEL computational evidence supports a deleterious effect, 0.666

BP6

Variant 2-218662989-C-T is Benign according to our data. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218662989-C-T is described in CliVar as Benign. Clinvar id is 136503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCS1L	NM_001079866.2 link	c.996C>T	p.Asn332Asn	synonymous_variant	Exon 7 of 8	ENST00000359273.8	NP_001073335.1	Q9Y276A0A024R445

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCS1L	ENST00000359273.8 link	c.996C>T	p.Asn332Asn	synonymous_variant	Exon 7 of 8	1	NM_001079866.2	ENSP00000352219.3		Q9Y276

Frequencies

GnomAD3 genomes

AF:

0.0555

AC:

8430

AN:

151816

Hom.:

329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0428

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0338

Gnomad OTH

AF:

0.0504

GnomAD2 exomes

AF:

0.0435

AC:

10939

AN:

251478

AF XY:

0.0426

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.0319

Gnomad EAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.0317

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0383

GnomAD4 exome

AF:

0.0376

AC:

55013

AN:

1461826

Hom.:

1310

Cov.:

AF XY:

0.0378

AC XY:

27485

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.107

AC:

3588

AN:

33480

American (AMR)

AF:

0.0219

AC:

978

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0328

AC:

856

AN:

26136

East Asian (EAS)

AF:

0.113

AC:

4468

AN:

39700

South Asian (SAS)

AF:

0.0425

AC:

3670

AN:

86256

European-Finnish (FIN)

AF:

0.0314

AC:

1678

AN:

53410

Middle Eastern (MID)

AF:

0.0302

AC:

174

AN:

5768

European-Non Finnish (NFE)

AF:

0.0333

AC:

37032

AN:

1111958

Other (OTH)

AF:

0.0425

AC:

2569

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

3403

6805

10208

13610

17013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1504

3008

4512

6016

7520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0556

AC:

8444

AN:

151934

Hom.:

330

Cov.:

AF XY:

0.0545

AC XY:

4047

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.104

AC:

4304

AN:

41376

American (AMR)

AF:

0.0311

AC:

475

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3468

East Asian (EAS)

AF:

0.119

AC:

614

AN:

5150

South Asian (SAS)

AF:

0.0428

AC:

205

AN:

4790

European-Finnish (FIN)

AF:

0.0273

AC:

289

AN:

10574

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0338

AC:

2300

AN:

67990

Other (OTH)

AF:

0.0499

AC:

105

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

379

758

1138

1517

1896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0423

Hom.:

144

Bravo

AF:

0.0585

Asia WGS

AF:

0.0700

AC:

241

AN:

3478

EpiCase

AF:

0.0340

EpiControl

AF:

0.0357

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 15, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GRACILE syndrome

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Asn332Asn in exon 8 of BCS1L: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 11.50% (994/8646) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs33946522). -

Feb 14, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mitochondrial complex III deficiency nuclear type 1

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pili torti-deafness syndrome

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Leigh syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.1

(source)

DANN

Benign

0.76

PhyloP100

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over