rs7234941

Variant names:

• chr18-63255618-C-T
• rs7234941
• NM_000633.3:c.585+62464G>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+62464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,086 control chromosomes in the GnomAD database, including 1,778 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 0.14 (1778 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+62464G>A		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+62464G>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+62464G>A		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22031 AN: 151968 Hom.: 1779 Cov.: 32

Gnomad AFR AF: 0.0899

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.145 AC: 22018 AN: 152086 Hom.: 1778 Cov.: 32 AF XY: 0.143 AC XY: 10655 AN XY: 74338

African (AFR) AF: 0.0896 AC: 3718 AN: 41476

American (AMR) AF: 0.122 AC: 1861 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3472

East Asian (EAS) AF: 0.164 AC: 852 AN: 5180

South Asian (SAS) AF: 0.100 AC: 485 AN: 4834

European-Finnish (FIN) AF: 0.172 AC: 1821 AN: 10564

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12397 AN: 67960

Other (OTH) AF: 0.156 AC: 330 AN: 2110

Alfa AF: 0.167 Hom.: 9345

Bravo AF: 0.138

Asia WGS AF: 0.112 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.96
DANN	Benign	0.57
PhyloP100		-0.17
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: rs7234941; hg19: chr18-60922851;