chr18-63127421-C-T

Variant names:

• chr18-63127421-C-T
• rs1564483
• NM_000633.3:c.*1204G>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.*1204G>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 0.23 in 235,960 control chromosomes in the GnomAD database, including 6,861 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 0.22 (4179 hom., cov: 32)
  • Exomes 𝑓: 0.25 (2682 hom.)
• Consequence: BCL2 NM_000633.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 44 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 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.*1204G>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.*1204G>A		3_prime_UTR	Exon 3 of 3	ENSP00000329623.3	P10415-1
	BCL2	ENST00000398117.1	TSL:1	c.*1204G>A		3_prime_UTR	Exon 2 of 2	ENSP00000381185.1	P10415-1
	BCL2	ENST00000678301.1		c.*1204G>A		3_prime_UTR	Exon 2 of 2	ENSP00000504546.1	A0A7I2V5Q9

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33524 AN: 152064 Hom.: 4181 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.249 AC: 20857 AN: 83778 Hom.: 2682 Cov.: 0 AF XY: 0.250 AC XY: 9712 AN XY: 38894

African (AFR) AF: 0.108 AC: 414 AN: 3822

American (AMR) AF: 0.153 AC: 385 AN: 2514

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 1123 AN: 5100

East Asian (EAS) AF: 0.292 AC: 3451 AN: 11804

South Asian (SAS) AF: 0.213 AC: 157 AN: 738

European-Finnish (FIN) AF: 0.251 AC: 184 AN: 734

Middle Eastern (MID) AF: 0.206 AC: 105 AN: 510

European-Non Finnish (NFE) AF: 0.260 AC: 13468 AN: 51742

Other (OTH) AF: 0.230 AC: 1570 AN: 6814

GnomAD4 genome AF: 0.220 AC: 33518 AN: 152182 Hom.: 4179 Cov.: 32 AF XY: 0.220 AC XY: 16399 AN XY: 74402

African (AFR) AF: 0.118 AC: 4879 AN: 41520

American (AMR) AF: 0.163 AC: 2495 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3472

East Asian (EAS) AF: 0.380 AC: 1967 AN: 5176

South Asian (SAS) AF: 0.228 AC: 1096 AN: 4816

European-Finnish (FIN) AF: 0.294 AC: 3112 AN: 10598

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18487 AN: 67994

Other (OTH) AF: 0.208 AC: 439 AN: 2114

Alfa AF: 0.249 Hom.: 9326

Bravo AF: 0.205

Asia WGS AF: 0.270 AC: 940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.047
DANN	Benign	0.62
PhyloP100		-2.3
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: rs1564483; hg19: chr18-60794654; COSMIC: COSV61373676;