rs3789068

Variant names:

• chr2-111151670-A-G
• rs3789068
• NM_138621.5:c.498+1523A>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.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
• Publications: 25 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=-0.89).
• 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 rank	MANE	Protein	UniProt
BCL2L11	NM_138621.5	c.498+1523A>G		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.498+1523A>G		intron_variant	Intron 3 of 3	1	NM_138621.5	ENSP00000376943.2

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

African (AFR) AF: 0.353 AC: 14629 AN: 41452

American (AMR) AF: 0.287 AC: 4390 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3468

East Asian (EAS) AF: 0.431 AC: 2227 AN: 5170

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4824

European-Finnish (FIN) AF: 0.490 AC: 5182 AN: 10578

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32341 AN: 67984

Other (OTH) AF: 0.378 AC: 799 AN: 2112

Alfa AF: 0.443 Hom.: 8391

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
PhyloP100		-1.4
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: rs3789068; hg19: chr2-111909247; COSMIC: COSV58028179;