22-17629087-C-A

Position:

• chr22-17629087-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000399782.5(BCL2L13):​c.-650+82C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 158,326 control chromosomes in the GnomAD database, including 538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (530 hom., cov: 32)
  • Exomes 𝑓: 0.042 (8 hom.)
• Consequence: BCL2L13 ENST00000399782.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.618

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]

BCL2L13 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 22-17629087-C-A is Benign according to our data. Variant chr22-17629087-C-A is described in ClinVar as [Benign]. Clinvar id is 1274797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L13	XM_011546119.2	c.-593+181C>A		intron_variant			XP_011544421.1
BCL2L13	XM_011546120.2	c.-593+153C>A		intron_variant			XP_011544422.1
BCL2L13	XM_047441286.1	c.-593+82C>A		intron_variant			XP_047297242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L13	ENST00000399782.5	c.-650+82C>A		intron_variant		1		ENSP00000382682.1
BCL2L13	ENST00000399781.5	n.52+181C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11674 AN: 151944 Hom.: 530 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0631

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0707

GnomAD4 exome AF: 0.0423 AC: 265 AN: 6264 Hom.: 8 AF XY: 0.0383 AC XY: 140 AN XY: 3660

Gnomad4 AFR exome AF: 0.0882

Gnomad4 AMR exome AF: 0.0293

Gnomad4 ASJ exome AF: 0.0395

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0332

Gnomad4 FIN exome AF: 0.0488

Gnomad4 NFE exome AF: 0.0565

Gnomad4 OTH exome AF: 0.0285

GnomAD4 genome AF: 0.0768 AC: 11685 AN: 152062 Hom.: 530 Cov.: 32 AF XY: 0.0733 AC XY: 5448 AN XY: 74342

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0440

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0276

Gnomad4 FIN AF: 0.0631

Gnomad4 NFE AF: 0.0748

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0261 Hom.: 11

Bravo AF: 0.0778

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.0
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs737993; hg19: chr22-18111853;