18-63127955-C-T

Variant names:

• chr18-63127955-C-T
• rs4987845
• NM_000633.3:c.*670G>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.*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
• Publications: 21 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]

ENSG00000299452 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.*670G>A		3_prime_UTR	Exon 3 of 3	NP_000624.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.*670G>A		3_prime_UTR	Exon 3 of 3	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.*670G>A		3_prime_UTR	Exon 2 of 2	ENSP00000381185.1
	BCL2	ENST00000677227.1		n.*911G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000504566.1

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

African (AFR) AF: 0.0193 AC: 66 AN: 3416

American (AMR) AF: 0.0511 AC: 111 AN: 2172

Ashkenazi Jewish (ASJ) AF: 0.0659 AC: 305 AN: 4628

East Asian (EAS) AF: 0.00133 AC: 14 AN: 10496

South Asian (SAS) AF: 0.0180 AC: 11 AN: 610

European-Finnish (FIN) AF: 0.0360 AC: 17 AN: 472

Middle Eastern (MID) AF: 0.108 AC: 47 AN: 436

European-Non Finnish (NFE) AF: 0.0941 AC: 4208 AN: 44716

Other (OTH) AF: 0.0763 AC: 465 AN: 6096

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

African (AFR) AF: 0.0162 AC: 673 AN: 41542

American (AMR) AF: 0.0635 AC: 971 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 232 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5194

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4824

European-Finnish (FIN) AF: 0.0478 AC: 507 AN: 10604

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0926 AC: 6295 AN: 68012

Other (OTH) AF: 0.0776 AC: 164 AN: 2114

Alfa AF: 0.0832 Hom.: 747

Bravo AF: 0.0597

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.69
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: rs4987845; hg19: chr18-60795188; COSMIC: COSV61371358;