rs10503078

Variant names:

• chr18-63132955-G-A
• rs10503078
• NM_000633.3:c.586-4196C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-63132955-G-A
• chr18-63132955-G-C

Variant summary

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

The NM_000633.3(BCL2):​c.586-4196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,130 control chromosomes in the GnomAD database, including 3,000 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 0.18 (3000 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-4196C>T		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-4196C>T		intron_variant	Intron 1 of 1		XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.586-4196C>T		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27752 AN: 152012 Hom.: 2986 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.183 AC: 27811 AN: 152130 Hom.: 3000 Cov.: 32 AF XY: 0.188 AC XY: 14005 AN XY: 74374

African (AFR) AF: 0.253 AC: 10509 AN: 41490

American (AMR) AF: 0.181 AC: 2768 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1995 AN: 5164

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4822

European-Finnish (FIN) AF: 0.177 AC: 1869 AN: 10578

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8189 AN: 67992

Other (OTH) AF: 0.159 AC: 335 AN: 2108

Alfa AF: 0.147 Hom.: 312

Bravo AF: 0.186

Asia WGS AF: 0.279 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.078
DANN	Benign	0.59
PhyloP100		-1.4
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: rs10503078; hg19: chr18-60800188;