rs3789068

chr2-111151670-A-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+1523A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,076 control chromosomes in the GnomAD database, including 13,400 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 0.41 (13400 hom., cov: 33)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L11	NM_138621.5	c.498+1523A>G		intron_variant		ENST00000393256.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L11	ENST00000393256.8	c.498+1523A>G		intron_variant		1	NM_138621.5	P1
MIR4435-2HG	ENST00000645030.2	n.453-114748T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62435 AN: 151958 Hom.: 13397 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.411 AC: 62453 AN: 152076 Hom.: 13400 Cov.: 33 AF XY: 0.405 AC XY: 30079 AN XY: 74342

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.378

Alfa AF: 0.441 Hom.: 7523

Bravo AF: 0.397

Asia WGS AF: 0.321 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.061
Dann	Benign	0.60

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: rs3789068; hg19: chr2-111909247; COSMIC: COSV58028179;