18-63257737-C-T

Variant names:

• chr18-63257737-C-T
• rs7226979
• NM_000633.3:c.585+60345G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):​c.585+60345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,998 control chromosomes in the GnomAD database, including 13,712 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 (13712 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+60345G>A		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+60345G>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+60345G>A		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63711 AN: 151880 Hom.: 13700 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.419 AC: 63753 AN: 151998 Hom.: 13712 Cov.: 32 AF XY: 0.416 AC XY: 30897 AN XY: 74272

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.421

Alfa AF: 0.434 Hom.: 4945

Bravo AF: 0.414

Asia WGS AF: 0.492 AC: 1710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.18
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs7226979; hg19: chr18-60924970;