Variant 2-218660503-AC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001079866.2(BCS1L):c.-49-435del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 170,624 control chromosomes in the GnomAD database, including 47 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 47 hom., cov: 32)

Exomes 𝑓: 0.00093 ( 0 hom. )

Consequence

BCS1L
NM_001079866.2 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0410

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-218660503-AC-A is Benign according to our data. Variant chr2-218660503-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 676726.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1887/152312) while in subpopulation AFR AF= 0.0434 (1802/41552). AF 95% confidence interval is 0.0417. There are 47 homozygotes in gnomad4. There are 884 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCS1L	NM_001079866.2 linkuse as main transcript	c.-49-435del		intron_variant		ENST00000359273.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCS1L	ENST00000359273.8 linkuse as main transcript	c.-49-435del		intron_variant		1	NM_001079866.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1881

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00621

GnomAD4 exome

AF:

0.000928

AC:

AN:

18312

Hom.:

Cov.:

AF XY:

0.000946

AC XY:

AN XY:

9518

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.00258

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.00256

GnomAD4 genome

AF:

0.0124

AC:

1887

AN:

152312

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

884

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0434

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00614

Bravo

AF:

0.0141

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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