rs17757541

Variant names:

• chr18-63212453-C-G
• rs17757541
• NM_000633.3:c.586-83694G>C

Your query was ambiguous. Multiple possible variants found:

• chr18-63212453-C-G
• chr18-63212453-C-T

Variant summary

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

The NM_000633.3(BCL2):​c.586-83694G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,654 control chromosomes in the GnomAD database, including 2,331 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 0.15 (2331 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 14 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]

ENSG00000308299 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 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.586-83694G>C		intron	N/A	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.586-83694G>C		intron	N/A	ENSP00000329623.3	P10415-1
	BCL2	ENST00000398117.1	TSL:1	c.586-83694G>C		intron	N/A	ENSP00000381185.1	P10415-1
	BCL2	ENST00000677227.1		n.*106+68434G>C		intron	N/A	ENSP00000504566.1	A0A7I2V5Q7

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22284 AN: 151538 Hom.: 2327 Cov.: 32

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.147 AC: 22296 AN: 151654 Hom.: 2331 Cov.: 32 AF XY: 0.150 AC XY: 11147 AN XY: 74080

African (AFR) AF: 0.0335 AC: 1390 AN: 41472

American (AMR) AF: 0.202 AC: 3062 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3468

East Asian (EAS) AF: 0.139 AC: 717 AN: 5172

South Asian (SAS) AF: 0.243 AC: 1174 AN: 4824

European-Finnish (FIN) AF: 0.213 AC: 2232 AN: 10492

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12372 AN: 67750

Other (OTH) AF: 0.155 AC: 324 AN: 2094

Alfa AF: 0.0720 Hom.: 119

Bravo AF: 0.142

Asia WGS AF: 0.186 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.5
DANN	Benign	0.62
PhyloP100		1.3
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: rs17757541; hg19: chr18-60879686; COSMIC: COSV107372262; COSMIC: COSV107372262;