rs12613243

Variant names:

• chr2-111139929-T-C
• rs12613243
• NM_138621.5:c.395-10115T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-111139929-T-C
• chr2-111139929-T-G

Variant summary

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

The NM_138621.5(BCL2L11):​c.395-10115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 152,316 control chromosomes in the GnomAD database, including 847 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 0.092 (847 hom., cov: 32)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L11	NM_138621.5	c.395-10115T>C		intron_variant	Intron 2 of 3	ENST00000393256.8	NP_619527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8	c.395-10115T>C		intron_variant	Intron 2 of 3	1	NM_138621.5	ENSP00000376943.2

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14015 AN: 152198 Hom.: 847 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0933

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0966

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

GnomAD4 genome AF: 0.0921 AC: 14029 AN: 152316 Hom.: 847 Cov.: 32 AF XY: 0.0930 AC XY: 6928 AN XY: 74480

African (AFR) AF: 0.159 AC: 6590 AN: 41562

American (AMR) AF: 0.0932 AC: 1426 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3470

East Asian (EAS) AF: 0.126 AC: 653 AN: 5176

South Asian (SAS) AF: 0.0724 AC: 350 AN: 4832

European-Finnish (FIN) AF: 0.0373 AC: 396 AN: 10624

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0609 AC: 4143 AN: 68030

Other (OTH) AF: 0.0951 AC: 201 AN: 2114

Alfa AF: 0.0659 Hom.: 563

Bravo AF: 0.100

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		-0.28
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: rs12613243; hg19: chr2-111897506;