chr18-63128308-C-T

Variant names:

• chr18-63128308-C-T
• rs4987843
• NM_000633.3:c.*317G>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.*317G>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 0.132 in 262,416 control chromosomes in the GnomAD database, including 3,171 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 0.15 (2375 hom., cov: 33)
  • Exomes 𝑓: 0.10 (796 hom.)
• Consequence: BCL2 NM_000633.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 12 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.*317G>A		3_prime_UTR	Exon 3 of 3	NP_000624.2	P10415-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.*317G>A		3_prime_UTR	Exon 3 of 3	ENSP00000329623.3	P10415-1
	BCL2	ENST00000398117.1	TSL:1	c.*317G>A		3_prime_UTR	Exon 2 of 2	ENSP00000381185.1	P10415-1
	BCL2	ENST00000678301.1		c.*317G>A		3_prime_UTR	Exon 2 of 2	ENSP00000504546.1	A0A7I2V5Q9

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23207 AN: 152134 Hom.: 2365 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.103 AC: 11341 AN: 110164 Hom.: 796 Cov.: 0 AF XY: 0.102 AC XY: 5399 AN XY: 53140

African (AFR) AF: 0.293 AC: 1318 AN: 4504

American (AMR) AF: 0.0972 AC: 352 AN: 3622

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 761 AN: 5946

East Asian (EAS) AF: 0.00150 AC: 19 AN: 12692

South Asian (SAS) AF: 0.0518 AC: 200 AN: 3860

European-Finnish (FIN) AF: 0.0775 AC: 167 AN: 2154

Middle Eastern (MID) AF: 0.179 AC: 109 AN: 610

European-Non Finnish (NFE) AF: 0.106 AC: 7269 AN: 68482

Other (OTH) AF: 0.138 AC: 1146 AN: 8294

GnomAD4 genome AF: 0.153 AC: 23235 AN: 152252 Hom.: 2375 Cov.: 33 AF XY: 0.147 AC XY: 10954 AN XY: 74464

African (AFR) AF: 0.298 AC: 12354 AN: 41516

American (AMR) AF: 0.113 AC: 1729 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0580 AC: 280 AN: 4826

European-Finnish (FIN) AF: 0.0867 AC: 920 AN: 10608

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6953 AN: 68016

Other (OTH) AF: 0.168 AC: 355 AN: 2116

Alfa AF: 0.127 Hom.: 2086

Bravo AF: 0.163

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		1.5
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: rs4987843; hg19: chr18-60795541;