rs11876772

Variant names:

• chr18-63150473-G-A
• rs11876772
• NM_000633.3:c.586-21714C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-63150473-G-A
• chr18-63150473-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.586-21714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,036 control chromosomes in the GnomAD database, including 27,218 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 0.59 (27218 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 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.586-21714C>T		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.586-21714C>T		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.586-21714C>T		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000678301.1		c.24+7600C>T		intron	N/A	ENSP00000504546.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89592 AN: 151916 Hom.: 27177 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.590 AC: 89683 AN: 152036 Hom.: 27218 Cov.: 32 AF XY: 0.587 AC XY: 43615 AN XY: 74314

African (AFR) AF: 0.734 AC: 30432 AN: 41484

American (AMR) AF: 0.525 AC: 8029 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3150 AN: 5150

South Asian (SAS) AF: 0.614 AC: 2963 AN: 4828

European-Finnish (FIN) AF: 0.487 AC: 5146 AN: 10568

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36181 AN: 67938

Other (OTH) AF: 0.582 AC: 1226 AN: 2108

Alfa AF: 0.556 Hom.: 29006

Bravo AF: 0.597

Asia WGS AF: 0.573 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.65
PhyloP100		-0.71
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: rs11876772; hg19: chr18-60817706;