chr18-63257380-A-T

Variant names:

• chr18-63257380-A-T
• rs1944419
• NM_000633.3:c.585+60702T>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+60702T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,182 control chromosomes in the GnomAD database, including 13,815 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 0.41 (13815 hom., cov: 33)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.670
• 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]

ENSG00000308299 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+60702T>A		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+60702T>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+60702T>A		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62663 AN: 152062 Hom.: 13805 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.412 AC: 62708 AN: 152182 Hom.: 13815 Cov.: 33 AF XY: 0.412 AC XY: 30655 AN XY: 74404

African (AFR) AF: 0.263 AC: 10933 AN: 41520

American (AMR) AF: 0.416 AC: 6366 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1749 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3047 AN: 5182

South Asian (SAS) AF: 0.611 AC: 2949 AN: 4826

European-Finnish (FIN) AF: 0.365 AC: 3868 AN: 10590

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

European-Non Finnish (NFE) AF: 0.476 AC: 32338 AN: 67984

Other (OTH) AF: 0.428 AC: 905 AN: 2116

Alfa AF: 0.433 Hom.: 1821

Bravo AF: 0.403

Asia WGS AF: 0.559 AC: 1941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		0.67
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: rs1944419; hg19: chr18-60924613;