rs2303561

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001079866.2(BCS1L):c.719+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,608,734 control chromosomes in the GnomAD database, including 161,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 24818 hom., cov: 32)

Exomes 𝑓: 0.42 ( 136411 hom. )

Consequence

BCS1L
NM_001079866.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.797

Publications

27 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen
GRACILE syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
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
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

BCS1L links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001079866.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-218662282-C-T is Benign according to our data. Variant chr2-218662282-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079866.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCS1L	NM_001079866.2	MANE Select	c.719+22C>T	intron	N/A	NP_001073335.1	Q9Y276
BCS1L	NM_001257342.2		c.719+22C>T	intron	N/A	NP_001244271.1	Q9Y276
BCS1L	NM_001257343.2		c.719+22C>T	intron	N/A	NP_001244272.1	A0A024R445

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCS1L	ENST00000359273.8	TSL:1 MANE Select	c.719+22C>T	intron	N/A	ENSP00000352219.3	Q9Y276
BCS1L	ENST00000392109.5	TSL:1	c.719+22C>T	intron	N/A	ENSP00000375957.1	Q9Y276
BCS1L	ENST00000392111.7	TSL:1	c.719+22C>T	intron	N/A	ENSP00000375959.2	Q9Y276

Frequencies

GnomAD3 genomes

AF:

0.533

AC:

80953

AN:

151916

Hom.:

24751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.852

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.481

GnomAD2 exomes

AF:

0.419

AC:

105259

AN:

251422

AF XY:

0.409

show subpopulations

Gnomad AFR exome

AF:

0.864

Gnomad AMR exome

AF:

0.403

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.433

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.424

AC:

617165

AN:

1456700

Hom.:

136411

Cov.:

AF XY:

0.419

AC XY:

303649

AN XY:

725060

show subpopulations

African (AFR)

AF:

0.873

AC:

29120

AN:

33350

American (AMR)

AF:

0.408

AC:

18233

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

10312

AN:

26100

East Asian (EAS)

AF:

0.175

AC:

6945

AN:

39670

South Asian (SAS)

AF:

0.331

AC:

28512

AN:

86144

European-Finnish (FIN)

AF:

0.429

AC:

22903

AN:

53392

Middle Eastern (MID)

AF:

0.366

AC:

2109

AN:

5766

European-Non Finnish (NFE)

AF:

0.427

AC:

473114

AN:

1107336

Other (OTH)

AF:

0.430

AC:

25917

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

18824

37648

56471

75295

94119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14442

28884

43326

57768

72210

<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:

0.533

AC:

81080

AN:

152034

Hom.:

24818

Cov.:

AF XY:

0.525

AC XY:

39031

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.852

AC:

35356

AN:

41474

American (AMR)

AF:

0.447

AC:

6824

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1388

AN:

3468

East Asian (EAS)

AF:

0.182

AC:

944

AN:

5174

South Asian (SAS)

AF:

0.326

AC:

1571

AN:

4824

European-Finnish (FIN)

AF:

0.429

AC:

4521

AN:

10550

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

29001

AN:

67956

Other (OTH)

AF:

0.481

AC:

1015

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1662

3325

4987

6650

8312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

668

1336

2004

2672

3340

<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:

0.471

Hom.:

7328

Bravo

AF:

0.551

Asia WGS

AF:

0.300

AC:

1046

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

(source)

DANN

Benign

0.72

PhyloP100

-0.80

PromoterAI

0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over