rs956572

chr18-63153338-A-Gchr18-63153338-A-T

Variant summary

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

The NM_000633.3(BCL2):c.586-24579T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,056 control chromosomes in the GnomAD database, including 31,966 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 0.64 (31966 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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 = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.586-24579T>C		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.586-24579T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.586-24579T>C		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97666 AN: 151938 Hom.: 31917 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.643 AC: 97768 AN: 152056 Hom.: 31966 Cov.: 32 AF XY: 0.641 AC XY: 47653 AN XY: 74306

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.651

Alfa AF: 0.608 Hom.: 37294

Bravo AF: 0.647

Asia WGS AF: 0.600 AC: 2090 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	0.77
Dann	Benign	0.36

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: rs956572; hg19: chr18-60820571;