rs10503077

chr18-63129212-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):c.586-453G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 152,118 control chromosomes in the GnomAD database, including 591 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 0.081 (591 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

Genes affected

BCL2 (HGNC:990): (BCL2 apoptosis regulator) This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.586-453G>A		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.586-453G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.586-453G>A		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.0811 AC: 12332 AN: 152006 Hom.: 581 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0556

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0524

Gnomad OTH AF: 0.0801

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0813 AC: 12367 AN: 152118 Hom.: 591 Cov.: 32 AF XY: 0.0812 AC XY: 6036 AN XY: 74362

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0672

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0556

Gnomad4 NFE AF: 0.0523

Gnomad4 OTH AF: 0.0792

Alfa AF: 0.0654 Hom.: 51

Bravo AF: 0.0863

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.20
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: rs10503077; hg19: chr18-60796445; COSMIC: COSV61372813;