rs1481031

Variant names:

• chr18-63184852-T-C
• rs1481031
• NM_000633.3:c.586-56093A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-63184852-T-C
• chr18-63184852-T-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.586-56093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,082 control chromosomes in the GnomAD database, including 24,184 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 0.54 (24184 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 12 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-56093A>G		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-56093A>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.586-56093A>G		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81890 AN: 151964 Hom.: 24184 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.539 AC: 81900 AN: 152082 Hom.: 24184 Cov.: 32 AF XY: 0.535 AC XY: 39744 AN XY: 74334

African (AFR) AF: 0.286 AC: 11873 AN: 41476

American (AMR) AF: 0.602 AC: 9205 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2281 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2741 AN: 5166

South Asian (SAS) AF: 0.510 AC: 2456 AN: 4814

European-Finnish (FIN) AF: 0.574 AC: 6052 AN: 10552

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45222 AN: 67998

Other (OTH) AF: 0.568 AC: 1198 AN: 2110

Alfa AF: 0.638 Hom.: 62242

Bravo AF: 0.533

Asia WGS AF: 0.489 AC: 1703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		0.21
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: rs1481031; hg19: chr18-60852085;