rs17484848

Variant names:

• chr2-111142983-T-C
• rs17484848
• NM_138621.5:c.395-7061T>C

Variant summary

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

The NM_138621.5(BCL2L11):​c.395-7061T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 152,278 control chromosomes in the GnomAD database, including 557 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 0.071 (557 hom., cov: 32)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659
• Publications: 20 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L11	NM_138621.5	c.395-7061T>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.395-7061T>C		intron_variant	Intron 2 of 3	1	NM_138621.5	ENSP00000376943.2

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10838 AN: 152160 Hom.: 558 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0741

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

GnomAD4 genome AF: 0.0711 AC: 10832 AN: 152278 Hom.: 557 Cov.: 32 AF XY: 0.0690 AC XY: 5138 AN XY: 74458

African (AFR) AF: 0.0168 AC: 697 AN: 41550

American (AMR) AF: 0.0522 AC: 799 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0213 AC: 103 AN: 4832

European-Finnish (FIN) AF: 0.0992 AC: 1051 AN: 10594

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7642 AN: 68020

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.111 Hom.: 149

Bravo AF: 0.0648

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.84
DANN	Benign	0.64
PhyloP100		-0.66
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: rs17484848; hg19: chr2-111900560;