chr22-17726847-A-G

Variant names:

• chr22-17726847-A-G
• rs4488761
• NM_015367.4:c.771A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015367.4(BCL2L13):​c.771A>G​(p.Ser257Ser) 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
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015367.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L13	NM_015367.4	MANE Select	c.771A>G	p.Ser257Ser	synonymous	Exon 7 of 7	NP_056182.2
	BCL2L13	NM_001270726.1		c.843A>G	p.Ser281Ser	synonymous	Exon 6 of 6	NP_001257655.1
	BCL2L13	NM_001270727.1		c.699A>G	p.Ser233Ser	synonymous	Exon 5 of 5	NP_001257656.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L13	ENST00000317582.10	TSL:1 MANE Select	c.771A>G	p.Ser257Ser	synonymous	Exon 7 of 7	ENSP00000318883.5
	BCL2L13	ENST00000399777.2	TSL:1	n.*269A>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000382677.2
	BCL2L13	ENST00000355028.4	TSL:1	c.*41A>G		3_prime_UTR	Exon 5 of 5	ENSP00000347133.3

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

GnomAD2 exomes AF: 0.596 AC: 149588 AN: 251064 AF XY: 0.591

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 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

African (AFR) AF: 0.597 AC: 20002 AN: 33480

American (AMR) AF: 0.678 AC: 30328 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 15291 AN: 26134

East Asian (EAS) AF: 0.949 AC: 37659 AN: 39700

South Asian (SAS) AF: 0.636 AC: 54852 AN: 86258

European-Finnish (FIN) AF: 0.502 AC: 26813 AN: 53412

Middle Eastern (MID) AF: 0.582 AC: 3358 AN: 5768

European-Non Finnish (NFE) AF: 0.527 AC: 585693 AN: 1111954

Other (OTH) AF: 0.570 AC: 34429 AN: 60394

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

African (AFR) AF: 0.600 AC: 24864 AN: 41464

American (AMR) AF: 0.640 AC: 9783 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2020 AN: 3472

East Asian (EAS) AF: 0.926 AC: 4793 AN: 5176

South Asian (SAS) AF: 0.644 AC: 3109 AN: 4826

European-Finnish (FIN) AF: 0.507 AC: 5351 AN: 10560

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35403 AN: 67970

Other (OTH) AF: 0.563 AC: 1188 AN: 2110

Alfa AF: 0.544 Hom.: 42387

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.81
DANN	Benign	0.63
PhyloP100		-0.63
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

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