rs58447305

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001079866.2(BCS1L):c.628G>A(p.Asp210Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,613,996 control chromosomes in the GnomAD database, including 1,415 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 677 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 738 hom. )

Consequence

BCS1L
NM_001079866.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 2.36

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016899705).

BP6

Variant 2-218661926-G-A is Benign according to our data. Variant chr2-218661926-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCS1L	NM_001079866.2 link	c.628G>A	p.Asp210Asn	missense_variant	Exon 4 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.628G>A	p.Asp210Asn	missense_variant	Exon 4 of 8	1	NM_001079866.2	ENSP00000352219.3		Q9Y276

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8519

AN:

152074

Hom.:

672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0276

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.0480

GnomAD3 exomes

AF:

0.0182

AC:

4579

AN:

251114

Hom.:

294

AF XY:

0.0146

AC XY:

1980

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00709

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00378

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.00864

AC:

12634

AN:

1461804

Hom.:

738

Cov.:

AF XY:

0.00811

AC XY:

5900

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.0156

Gnomad4 ASJ exome

AF:

0.0166

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00723

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.0192

GnomAD4 genome

AF:

0.0562

AC:

8552

AN:

152192

Hom.:

677

Cov.:

AF XY:

0.0536

AC XY:

3989

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0276

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00891

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00350

Gnomad4 OTH

AF:

0.0480

Alfa

AF:

0.0107

Hom.:

144

Bravo

AF:

0.0641

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.182

AC:

803

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.0214

AC:

2603

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00563

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 09, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 15, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

GRACILE syndrome

Benign:3

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

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

Dec 09, 2011

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. -

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.Asp210Asn in exon 5 of BCS1L: This variant is not expected to have clinical si gnificance because it has been identified in 23.75% (314/1322) of African chromo somes by the 1000 Genomes Project (Phase 3; dbSNP rs58447305). -

Mitochondrial complex III deficiency nuclear type 1

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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

- -

Leigh syndrome

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.13

.;T;T;T;T;T;T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.027

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.87

D;.;.;.;.;.;.;D

MetaRNN

Benign

0.0017

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.54

.;N;N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.73

N;N;N;N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.63

T;T;T;T;T;T;T;T

Sift4G

Benign

0.59

T;T;T;T;T;T;T;T

Polyphen

0.0020

.;B;B;B;B;B;B;B

Vest4

0.12, 0.13, 0.078, 0.077, 0.076

MPC

0.59

ClinPred

0.013

GERP RS

4.8

Varity_R

0.11

gMVP

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over