2-111137967-C-G

Position:

• chr2-111137967-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138621.5(BCL2L11):​c.395-12077C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 150,644 control chromosomes in the GnomAD database, including 39,393 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 0.71 (39393 hom., cov: 28)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L11	NM_138621.5	c.395-12077C>G		intron_variant		ENST00000393256.8	NP_619527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8	c.395-12077C>G		intron_variant		1	NM_138621.5	ENSP00000376943.2

Frequencies

GnomAD3 genomes AF: 0.713 AC: 107301 AN: 150544 Hom.: 39349 Cov.: 28

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.713 AC: 107390 AN: 150644 Hom.: 39393 Cov.: 28 AF XY: 0.707 AC XY: 51913 AN XY: 73452

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.664

Alfa AF: 0.696 Hom.: 4404

Bravo AF: 0.715

Asia WGS AF: 0.682 AC: 2369 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs10204044; hg19: chr2-111895544;