18-63126261-C-T

Position:

• chr18-63126261-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.*2364G>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 0.0629 in 220,032 control chromosomes in the GnomAD database, including 580 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 (367 hom., cov: 32)
  • Exomes 𝑓: 0.071 (213 hom.)
• Consequence: BCL2 NM_000633.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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]

BCL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.*2364G>A		3_prime_UTR_variant	3/3	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.*2364G>A		3_prime_UTR_variant	2/2		XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.*2364G>A		3_prime_UTR_variant	3/3	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9041 AN: 151994 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.0770

GnomAD4 exome AF: 0.0706 AC: 4794 AN: 67920 Hom.: 213 Cov.: 0 AF XY: 0.0711 AC XY: 2241 AN XY: 31532

Gnomad4 AFR exome AF: 0.0213

Gnomad4 AMR exome AF: 0.0517

Gnomad4 ASJ exome AF: 0.0644

Gnomad4 EAS exome AF: 0.000901

Gnomad4 SAS exome AF: 0.0136

Gnomad4 FIN exome AF: 0.0366

Gnomad4 NFE exome AF: 0.0932

Gnomad4 OTH exome AF: 0.0732

GnomAD4 genome AF: 0.0594 AC: 9043 AN: 152112 Hom.: 367 Cov.: 32 AF XY: 0.0570 AC XY: 4241 AN XY: 74360

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0635

Gnomad4 ASJ AF: 0.0663

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0227

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0928

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0386 Hom.: 37

Bravo AF: 0.0599

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	-0.85
CADD	Benign	7.7
DANN	Benign	0.73

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: rs4987856; hg19: chr18-60793494; COSMIC: COSV61371332; COSMIC: COSV61371332;