rs616130

Positions:

• chr2-111155104-C-A
• chr2-111155104-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.498+4957C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,086 control chromosomes in the GnomAD database, including 27,991 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 0.58 (27991 hom., cov: 33)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L11	NM_138621.5	c.498+4957C>A		intron_variant		ENST00000393256.8	NP_619527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8	c.498+4957C>A		intron_variant		1	NM_138621.5	ENSP00000376943	P1
MIR4435-2HG	ENST00000645030.2	n.453-118182G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88840 AN: 151968 Hom.: 27945 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.585 AC: 88938 AN: 152086 Hom.: 27991 Cov.: 33 AF XY: 0.575 AC XY: 42719 AN XY: 74344

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.521

Alfa AF: 0.521 Hom.: 9862

Bravo AF: 0.591

Asia WGS AF: 0.411 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.56

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: rs616130; hg19: chr2-111912681; COSMIC: COSV58032186; COSMIC: COSV58032186;