22-17629087-C-T

Variant names:

• chr22-17629087-C-T
• rs737993
• ENST00000399782.5:c.-650+82C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000399782.5(BCL2L13):​c.-650+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 6,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: BCL2L13 ENST00000399782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L13	XM_011546119.2	c.-593+181C>T		intron_variant	Intron 1 of 6		XP_011544421.1
BCL2L13	XM_011546120.2	c.-593+153C>T		intron_variant	Intron 1 of 6		XP_011544422.1
BCL2L13	XM_047441286.1	c.-593+82C>T		intron_variant	Intron 1 of 6		XP_047297242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L13	ENST00000399782.5	c.-650+82C>T		intron_variant	Intron 1 of 6	1		ENSP00000382682.1
BCL2L13	ENST00000399781.5	n.52+181C>T		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.000159 AC: 1 AN: 6278 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3666

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 170

American (AMR) AF: 0.00 AC: 0 AN: 990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 76

East Asian (EAS) AF: 0.00 AC: 0 AN: 366

South Asian (SAS) AF: 0.00 AC: 0 AN: 1604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 82

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.000366 AC: 1 AN: 2734

Other (OTH) AF: 0.00 AC: 0 AN: 246

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.7
DANN	Benign	0.91
PhyloP100		0.62
PromoterAI		-0.045	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs737993; hg19: chr22-18111853;