rs1982673

Variant names:

• chr18-63130782-A-C
• rs1982673
• NM_000633.3:c.586-2023T>G

Your query was ambiguous. Multiple possible variants found:

• chr18-63130782-A-C
• chr18-63130782-A-G
• chr18-63130782-A-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.586-2023T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,100 control chromosomes in the GnomAD database, including 2,850 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 0.18 (2850 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• Publications: 13 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-2023T>G		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-2023T>G		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.586-2023T>G		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27540 AN: 151982 Hom.: 2839 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.181 AC: 27580 AN: 152100 Hom.: 2850 Cov.: 32 AF XY: 0.189 AC XY: 14041 AN XY: 74360

African (AFR) AF: 0.167 AC: 6934 AN: 41496

American (AMR) AF: 0.211 AC: 3218 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2220 AN: 5164

South Asian (SAS) AF: 0.367 AC: 1769 AN: 4824

European-Finnish (FIN) AF: 0.202 AC: 2133 AN: 10580

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10086 AN: 67994

Other (OTH) AF: 0.160 AC: 338 AN: 2108

Alfa AF: 0.161 Hom.: 6962

Bravo AF: 0.180

Asia WGS AF: 0.300 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.87
PhyloP100		0.99
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: rs1982673; hg19: chr18-60798015;