18-63126688-T-C

Variant names:

• chr18-63126688-T-C
• rs4987852
• NM_000633.3:c.*1937A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):​c.*1937A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 226,854 control chromosomes in the GnomAD database, including 416 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 0.049 (292 hom., cov: 33)
  • Exomes 𝑓: 0.050 (124 hom.)
• Consequence: BCL2 NM_000633.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 37 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 (NFE) allele frequency at 95% confidence interval = 0.0652 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.*1937A>G		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.*1937A>G		3_prime_UTR	Exon 3 of 3	ENSP00000329623.3	P10415-1
	BCL2	ENST00000398117.1	TSL:1	c.*1937A>G		3_prime_UTR	Exon 2 of 2	ENSP00000381185.1	P10415-1
	BCL2	ENST00000678301.1		c.*1937A>G		3_prime_UTR	Exon 2 of 2	ENSP00000504546.1	A0A7I2V5Q9

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7512 AN: 152134 Hom.: 292 Cov.: 33

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0454

GnomAD4 exome AF: 0.0495 AC: 3694 AN: 74602 Hom.: 124 Cov.: 0 AF XY: 0.0503 AC XY: 1732 AN XY: 34446

African (AFR) AF: 0.00868 AC: 31 AN: 3570

American (AMR) AF: 0.0290 AC: 66 AN: 2272

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 232 AN: 4706

East Asian (EAS) AF: 0.000659 AC: 7 AN: 10624

South Asian (SAS) AF: 0.0140 AC: 9 AN: 644

European-Finnish (FIN) AF: 0.0833 AC: 4 AN: 48

Middle Eastern (MID) AF: 0.0149 AC: 7 AN: 470

European-Non Finnish (NFE) AF: 0.0656 AC: 3018 AN: 46018

Other (OTH) AF: 0.0512 AC: 320 AN: 6250

GnomAD4 genome AF: 0.0493 AC: 7512 AN: 152252 Hom.: 292 Cov.: 33 AF XY: 0.0518 AC XY: 3854 AN XY: 74428

African (AFR) AF: 0.0123 AC: 512 AN: 41548

American (AMR) AF: 0.0448 AC: 685 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4828

European-Finnish (FIN) AF: 0.129 AC: 1363 AN: 10580

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4546 AN: 68018

Other (OTH) AF: 0.0449 AC: 95 AN: 2116

Alfa AF: 0.0569 Hom.: 973

Bravo AF: 0.0400

Asia WGS AF: 0.00837 AC: 29 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	12
DANN	Benign	0.83
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4987852; hg19: chr18-60793921;