rs4941185

Variant names:

• chr18-63156321-A-G
• rs4941185
• NM_000633.3:c.586-27562T>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.586-27562T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,058 control chromosomes in the GnomAD database, including 10,287 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 0.35 (10287 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.586-27562T>C		intron	N/A	NP_000624.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.586-27562T>C		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.586-27562T>C		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000678301.1		c.24+1752T>C		intron	N/A	ENSP00000504546.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52704 AN: 151940 Hom.: 10278 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.347 AC: 52729 AN: 152058 Hom.: 10287 Cov.: 32 AF XY: 0.349 AC XY: 25911 AN XY: 74318

African (AFR) AF: 0.153 AC: 6366 AN: 41500

American (AMR) AF: 0.467 AC: 7128 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3466

East Asian (EAS) AF: 0.540 AC: 2790 AN: 5168

South Asian (SAS) AF: 0.446 AC: 2144 AN: 4806

European-Finnish (FIN) AF: 0.386 AC: 4082 AN: 10576

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27684 AN: 67952

Other (OTH) AF: 0.345 AC: 730 AN: 2116

Alfa AF: 0.394 Hom.: 30467

Bravo AF: 0.344

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.76
DANN	Benign	0.63
PhyloP100		-0.80
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: rs4941185; hg19: chr18-60823554;