18-63127955-C-T

Position:

• chr18-63127955-C-T

Variant summary

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

The NM_000633.3(BCL2):​c.*670G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 225,312 control chromosomes in the GnomAD database, including 605 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 0.059 (369 hom., cov: 33)
  • Exomes 𝑓: 0.072 (236 hom.)
• Consequence: BCL2 NM_000633.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.*670G>A		3_prime_UTR_variant	3/3	ENST00000333681.5
BCL2	XM_047437733.1	c.*670G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.*670G>A		3_prime_UTR_variant	3/3	1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9025 AN: 152152 Hom.: 369 Cov.: 33

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.0765

GnomAD4 exome AF: 0.0718 AC: 5244 AN: 73042 Hom.: 236 Cov.: 0 AF XY: 0.0727 AC XY: 2455 AN XY: 33790

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.0511

Gnomad4 ASJ exome AF: 0.0659

Gnomad4 EAS exome AF: 0.00133

Gnomad4 SAS exome AF: 0.0180

Gnomad4 FIN exome AF: 0.0360

Gnomad4 NFE exome AF: 0.0941

Gnomad4 OTH exome AF: 0.0763

GnomAD4 genome AF: 0.0593 AC: 9027 AN: 152270 Hom.: 369 Cov.: 33 AF XY: 0.0570 AC XY: 4242 AN XY: 74460

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0635

Gnomad4 ASJ AF: 0.0668

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.0478

Gnomad4 NFE AF: 0.0926

Gnomad4 OTH AF: 0.0776

Alfa AF: 0.0858 Hom.: 586

Bravo AF: 0.0597

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.69

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: rs4987845; hg19: chr18-60795188; COSMIC: COSV61371358; COSMIC: COSV61371358;