18-63299164-C-T

Variant names:

• chr18-63299164-C-T
• rs2850761
• NM_000633.3:c.585+18918G>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+18918G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,222 control chromosomes in the GnomAD database, including 15,735 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 0.42 (15735 hom., cov: 33)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+18918G>A		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+18918G>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+18918G>A		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63546 AN: 152104 Hom.: 15719 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.418 AC: 63584 AN: 152222 Hom.: 15735 Cov.: 33 AF XY: 0.419 AC XY: 31167 AN XY: 74416

African (AFR) AF: 0.152 AC: 6326 AN: 41558

American (AMR) AF: 0.476 AC: 7278 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1596 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1292 AN: 5178

South Asian (SAS) AF: 0.420 AC: 2026 AN: 4824

European-Finnish (FIN) AF: 0.573 AC: 6062 AN: 10586

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37242 AN: 67994

Other (OTH) AF: 0.447 AC: 944 AN: 2114

Alfa AF: 0.505 Hom.: 86376

Bravo AF: 0.399

Asia WGS AF: 0.311 AC: 1082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.51
PhyloP100		0.28
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: rs2850761; hg19: chr18-60966397;