Variant chr2-218660284-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001079866.2(BCS1L):c.-50+541G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 152,592 control chromosomes in the GnomAD database, including 333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.056 ( 333 hom., cov: 32)

Exomes 𝑓: 0.020 ( 0 hom. )

Consequence

BCS1L
NM_001079866.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.215

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 -10 ACMG points.

BP6

Variant 2-218660284-G-A is Benign according to our data. Variant chr2-218660284-G-A is described in ClinVar as [Benign]. Clinvar id is 673726.Status of the report is criteria_provided_single_submitter, 1 stars.

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/exons	MANE	UniProt
BCS1L	NM_001079866.2 linkuse as main transcript	c.-50+541G>A		intron_variant		ENST00000359273.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCS1L	ENST00000359273.8 linkuse as main transcript	c.-50+541G>A		intron_variant		1	NM_001079866.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0557

AC:

8471

AN:

152130

Hom.:

332

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:

0.0436

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0339

Gnomad OTH

AF:

0.0504

GnomAD4 exome

AF:

0.0203

AC:

AN:

344

Hom.:

Cov.:

AF XY:

0.0253

AC XY:

AN XY:

198

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.0177

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0557

AC:

8485

AN:

152248

Hom.:

333

Cov.:

AF XY:

0.0547

AC XY:

4073

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0311

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0437

Gnomad4 FIN

AF:

0.0272

Gnomad4 NFE

AF:

0.0339

Gnomad4 OTH

AF:

0.0499

Alfa

AF:

0.0434

Hom.:

Bravo

AF:

0.0585

Asia WGS

AF:

0.0690

AC:

240

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GRACILE syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 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

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.9

DANN

Benign

0.67

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 23

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