rs686952

Variant names:

• chr2-111161769-A-C
• rs686952
• NM_138621.5:c.499-2364A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-111161769-A-C
• chr2-111161769-A-G
• chr2-111161769-A-T

Variant summary

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

The NM_138621.5(BCL2L11):​c.499-2364A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,136 control chromosomes in the GnomAD database, including 44,527 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 0.75 (44527 hom., cov: 32)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 9 publications found

Genes affected

BCL2L11 (HGNC:994): (BCL2 like 11) The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013]

MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

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 (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L11	NM_138621.5	c.499-2364A>C		intron_variant	Intron 3 of 3	ENST00000393256.8	NP_619527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8	c.499-2364A>C		intron_variant	Intron 3 of 3	1	NM_138621.5	ENSP00000376943.2

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114756 AN: 152018 Hom.: 44477 Cov.: 32

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.755 AC: 114851 AN: 152136 Hom.: 44527 Cov.: 32 AF XY: 0.750 AC XY: 55766 AN XY: 74374

African (AFR) AF: 0.933 AC: 38731 AN: 41516

American (AMR) AF: 0.629 AC: 9622 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2194 AN: 3470

East Asian (EAS) AF: 0.864 AC: 4472 AN: 5176

South Asian (SAS) AF: 0.573 AC: 2762 AN: 4822

European-Finnish (FIN) AF: 0.702 AC: 7411 AN: 10560

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47366 AN: 67990

Other (OTH) AF: 0.704 AC: 1485 AN: 2110

Alfa AF: 0.704 Hom.: 68167

Bravo AF: 0.761

Asia WGS AF: 0.705 AC: 2453 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	0.38
DANN	Benign	0.74
PhyloP100		-0.91
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: rs686952; hg19: chr2-111919346;