rs1893806

Variant names:

• chr18-63317731-C-A
• rs1893806
• NM_000633.3:c.585+351G>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+351G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,122,050 control chromosomes in the GnomAD database, including 153,116 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 0.45 (16759 hom., cov: 31)
  • Exomes 𝑓: 0.53 (136357 hom.)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 8 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+351G>T		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+351G>T		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67797 AN: 151672 Hom.: 16748 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.526 AC: 510431 AN: 970260 Hom.: 136357 Cov.: 33 AF XY: 0.526 AC XY: 238355 AN XY: 452762

African (AFR) AF: 0.194 AC: 4069 AN: 20940

American (AMR) AF: 0.609 AC: 3303 AN: 5426

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 4683 AN: 11346

East Asian (EAS) AF: 0.378 AC: 5975 AN: 15820

South Asian (SAS) AF: 0.422 AC: 9270 AN: 21990

European-Finnish (FIN) AF: 0.541 AC: 3083 AN: 5696

Middle Eastern (MID) AF: 0.491 AC: 1191 AN: 2426

European-Non Finnish (NFE) AF: 0.542 AC: 460501 AN: 849522

Other (OTH) AF: 0.495 AC: 18356 AN: 37094

GnomAD4 genome AF: 0.447 AC: 67833 AN: 151790 Hom.: 16759 Cov.: 31 AF XY: 0.449 AC XY: 33296 AN XY: 74134

African (AFR) AF: 0.222 AC: 9200 AN: 41352

American (AMR) AF: 0.567 AC: 8654 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1445 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2081 AN: 5156

South Asian (SAS) AF: 0.415 AC: 1990 AN: 4792

European-Finnish (FIN) AF: 0.544 AC: 5731 AN: 10530

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 36987 AN: 67912

Other (OTH) AF: 0.481 AC: 1015 AN: 2108

Alfa AF: 0.485 Hom.: 2858

Bravo AF: 0.442

Asia WGS AF: 0.388 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.49
PhyloP100		-0.023
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: rs1893806; hg19: chr18-60984964;