rs2046137

Variant names:

• chr18-63144897-T-C
• rs2046137
• NM_000633.3:c.586-16138A>G

Variant summary

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

The NM_000633.3(BCL2):​c.586-16138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,116 control chromosomes in the GnomAD database, including 4,660 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 0.23 (4660 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-16138A>G		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-16138A>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.586-16138A>G		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34312 AN: 151998 Hom.: 4640 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.226 AC: 34381 AN: 152116 Hom.: 4660 Cov.: 32 AF XY: 0.234 AC XY: 17423 AN XY: 74382

African (AFR) AF: 0.277 AC: 11499 AN: 41480

American (AMR) AF: 0.247 AC: 3773 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3067 AN: 5172

South Asian (SAS) AF: 0.437 AC: 2109 AN: 4828

European-Finnish (FIN) AF: 0.205 AC: 2168 AN: 10578

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10454 AN: 67978

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.206 Hom.: 1298

Bravo AF: 0.229

Asia WGS AF: 0.436 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.43
PhyloP100		-1.2
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: rs2046137; hg19: chr18-60812130;