2-111152165-C-A

Variant names:

• chr2-111152165-C-A
• rs17041883
• NM_138621.5:c.498+2018C>A

Variant summary

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

The ENST00000393256.8(BCL2L11):​c.498+2018C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,206 control chromosomes in the GnomAD database, including 1,166 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 0.12 (1166 hom., cov: 32)
• Consequence: BCL2L11 ENST00000393256.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393256.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	NM_138621.5	MANE Select	c.498+2018C>A		intron	N/A	NP_619527.1
	BCL2L11	NM_001204108.1		c.498+2018C>A		intron	N/A	NP_001191037.1
	BCL2L11	NM_138622.4		c.499-1615C>A		intron	N/A	NP_619528.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	ENST00000393256.8	TSL:1 MANE Select	c.498+2018C>A		intron	N/A	ENSP00000376943.2
	BCL2L11	ENST00000361493.10	TSL:1	n.*116+2018C>A		intron	N/A	ENSP00000354879.6
	BCL2L11	ENST00000415458.5	TSL:1	n.215-1615C>A		intron	N/A	ENSP00000393781.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17562 AN: 152088 Hom.: 1162 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0790

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

GnomAD4 genome AF: 0.116 AC: 17581 AN: 152206 Hom.: 1166 Cov.: 32 AF XY: 0.113 AC XY: 8384 AN XY: 74404

African (AFR) AF: 0.105 AC: 4351 AN: 41534

American (AMR) AF: 0.0682 AC: 1043 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1338 AN: 5168

South Asian (SAS) AF: 0.0673 AC: 325 AN: 4826

European-Finnish (FIN) AF: 0.132 AC: 1401 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8670 AN: 67998

Other (OTH) AF: 0.0839 AC: 177 AN: 2110

Alfa AF: 0.118 Hom.: 3207

Bravo AF: 0.113

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.73
PhyloP100		-0.19
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: rs17041883; hg19: chr2-111909742; COSMIC: COSV107351003;