2-111137143-T-C

Variant names:

• chr2-111137143-T-C
• rs17041868
• NM_138621.5:c.395-12901T>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.395-12901T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,228 control chromosomes in the GnomAD database, including 834 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 0.092 (834 hom., cov: 32)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 11 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 (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138621.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	NM_138621.5	MANE Select	c.395-12901T>C		intron	N/A	NP_619527.1	O43521-1
	BCL2L11	NM_001204108.1		c.395-12901T>C		intron	N/A	NP_001191037.1	O43521-8
	BCL2L11	NM_138622.4		c.395-12901T>C		intron	N/A	NP_619528.1	O43521-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	ENST00000393256.8	TSL:1 MANE Select	c.395-12901T>C		intron	N/A	ENSP00000376943.2	O43521-1
	BCL2L11	ENST00000361493.10	TSL:1	n.*12+6896T>C		intron	N/A	ENSP00000354879.6	A0A0C4DH20
	BCL2L11	ENST00000415458.5	TSL:1	n.214+13004T>C		intron	N/A	ENSP00000393781.1	O43521-16

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13965 AN: 152110 Hom.: 833 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0936

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0991

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

GnomAD4 genome AF: 0.0918 AC: 13980 AN: 152228 Hom.: 834 Cov.: 32 AF XY: 0.0928 AC XY: 6909 AN XY: 74434

African (AFR) AF: 0.156 AC: 6457 AN: 41504

American (AMR) AF: 0.0935 AC: 1431 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3472

East Asian (EAS) AF: 0.128 AC: 661 AN: 5176

South Asian (SAS) AF: 0.0725 AC: 350 AN: 4828

European-Finnish (FIN) AF: 0.0372 AC: 395 AN: 10616

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0618 AC: 4203 AN: 68014

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.0807 Hom.: 235

Bravo AF: 0.0997

Asia WGS AF: 0.0790 AC: 274 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	1.9
DANN	Benign	0.77
PhyloP100		-0.30
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: rs17041868; hg19: chr2-111894720;