rs4987852

Positions:

• chr18-63126688-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.*1937A>G		3_prime_UTR_variant	3/3	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.*1937A>G		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.*1937A>G		3_prime_UTR_variant	3/3	1	NM_000633.3	ENSP00000329623.3

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

Gnomad4 AFR exome AF: 0.00868

Gnomad4 AMR exome AF: 0.0290

Gnomad4 ASJ exome AF: 0.0493

Gnomad4 EAS exome AF: 0.000659

Gnomad4 SAS exome AF: 0.0140

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.0656

Gnomad4 OTH exome AF: 0.0512

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

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0448

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0596 Hom.: 443

Bravo AF: 0.0400

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs4987852; hg19: chr18-60793921;