rs4488761

Positions:

• chr22-17726847-A-G
• chr22-17726847-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015367.4(BCL2L13):​c.771A>G​(p.Ser257=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,613,882 control chromosomes in the GnomAD database, including 254,484 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25690 hom., cov: 32)
  • Exomes 𝑓: 0.55 (228794 hom.)
• Consequence: BCL2L13 NM_015367.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

Genes affected

BCL2L13 (HGNC:17164): (BCL2 like 13) This gene encodes a mitochondrially-localized protein with conserved B-cell lymphoma 2 homology motifs. Overexpression of the encoded protein results in apoptosis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-0.629 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L13	NM_015367.4	c.771A>G	p.Ser257=	synonymous_variant	7/7	ENST00000317582.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L13	ENST00000317582.10	c.771A>G	p.Ser257=	synonymous_variant	7/7	1	NM_015367.4	A2

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87139 AN: 151958 Hom.: 25673 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.560

GnomAD3 exomes AF: 0.596 AC: 149588 AN: 251064 Hom.: 46227 AF XY: 0.591 AC XY: 80179 AN XY: 135708

Gnomad AFR exome AF: 0.603

Gnomad AMR exome AF: 0.682

Gnomad ASJ exome AF: 0.581

Gnomad EAS exome AF: 0.927

Gnomad SAS exome AF: 0.639

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.522

Gnomad OTH exome AF: 0.575

GnomAD4 exome AF: 0.553 AC: 808425 AN: 1461806 Hom.: 228794 Cov.: 66 AF XY: 0.555 AC XY: 403283 AN XY: 727202

Gnomad4 AFR exome AF: 0.597

Gnomad4 AMR exome AF: 0.678

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.949

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.570

GnomAD4 genome AF: 0.573 AC: 87208 AN: 152076 Hom.: 25690 Cov.: 32 AF XY: 0.577 AC XY: 42932 AN XY: 74344

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.563

Alfa AF: 0.540 Hom.: 33797

Bravo AF: 0.587

Asia WGS AF: 0.764 AC: 2657 AN: 3478

EpiCase AF: 0.528

EpiControl AF: 0.530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.81
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs4488761; hg19: chr22-18209613; COSMIC: COSV58225684;