18-63227313-G-A

Variant names:

• chr18-63227313-G-A
• rs9959874
• NM_000633.3:c.585+90769C>T

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+90769C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 152,258 control chromosomes in the GnomAD database, including 572 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 0.085 (572 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 7 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=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+90769C>T		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+90769C>T		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+90769C>T		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12848 AN: 152140 Hom.: 568 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.0845 AC: 12871 AN: 152258 Hom.: 572 Cov.: 32 AF XY: 0.0869 AC XY: 6471 AN XY: 74438

African (AFR) AF: 0.0957 AC: 3973 AN: 41534

American (AMR) AF: 0.0872 AC: 1334 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3470

East Asian (EAS) AF: 0.113 AC: 588 AN: 5182

South Asian (SAS) AF: 0.162 AC: 781 AN: 4828

European-Finnish (FIN) AF: 0.0931 AC: 987 AN: 10596

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0689 AC: 4685 AN: 68030

Other (OTH) AF: 0.0856 AC: 181 AN: 2114

Alfa AF: 0.0757 Hom.: 79

Bravo AF: 0.0837

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.6
DANN	Benign	0.86
PhyloP100		0.34
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: rs9959874; hg19: chr18-60894546;