22-17629043-A-G

Position:

• chr22-17629043-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000399782.5(BCL2L13):​c.-650+38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00344 in 225,430 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (0 hom.)
• Consequence: BCL2L13 ENST00000399782.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.632

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 22-17629043-A-G is Benign according to our data. Variant chr22-17629043-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1193481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00469 (714/152258) while in subpopulation AFR AF= 0.0163 (678/41554). AF 95% confidence interval is 0.0153. There are 4 homozygotes in gnomad4. There are 326 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L13	XM_011546119.2	c.-593+137A>G		intron_variant			XP_011544421.1
BCL2L13	XM_011546120.2	c.-593+109A>G		intron_variant			XP_011544422.1
BCL2L13	XM_047441286.1	c.-593+38A>G		intron_variant			XP_047297242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L13	ENST00000399782.5	c.-650+38A>G		intron_variant		1		ENSP00000382682.1
BCL2L13	ENST00000399781.5	n.52+137A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 712 AN: 152140 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.000847 AC: 62 AN: 73172 Hom.: 0 Cov.: 0 AF XY: 0.000733 AC XY: 29 AN XY: 39566

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.000413

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000767

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000765

Gnomad4 OTH exome AF: 0.000288

GnomAD4 genome AF: 0.00469 AC: 714 AN: 152258 Hom.: 4 Cov.: 32 AF XY: 0.00438 AC XY: 326 AN XY: 74454

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00331

Bravo AF: 0.00550

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.57
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77803842; hg19: chr22-18111809;