18-63252097-A-T

Variant names:

• chr18-63252097-A-T
• rs9807663
• NM_000633.3:c.585+65985T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):​c.585+65985T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,202 control chromosomes in the GnomAD database, including 52,577 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 0.82 (52577 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 6 publications found

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]

ENSG00000308299 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+65985T>A		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+65985T>A		intron_variant	Intron 1 of 1		XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+65985T>A		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124840 AN: 152084 Hom.: 52538 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.821 AC: 124935 AN: 152202 Hom.: 52577 Cov.: 32 AF XY: 0.824 AC XY: 61330 AN XY: 74412

African (AFR) AF: 0.632 AC: 26229 AN: 41474

American (AMR) AF: 0.852 AC: 13044 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3111 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3248 AN: 5164

South Asian (SAS) AF: 0.888 AC: 4292 AN: 4832

European-Finnish (FIN) AF: 0.938 AC: 9951 AN: 10612

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62262 AN: 68026

Other (OTH) AF: 0.816 AC: 1725 AN: 2114

Alfa AF: 0.863 Hom.: 3379

Bravo AF: 0.804

Asia WGS AF: 0.770 AC: 2677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		-0.094
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9807663; hg19: chr18-60919330;