2-111150114-T-C

Variant names:

• chr2-111150114-T-C
• rs724710
• NM_138621.5:c.465T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138621.5(BCL2L11):​c.465T>C​(p.Ile155Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,613,482 control chromosomes in the GnomAD database, including 373,640 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 0.69 (37091 hom., cov: 33)
  • Exomes 𝑓: 0.67 (336549 hom.)
• Consequence: BCL2L11 NM_138621.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 60 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-1.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 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.465T>C	p.Ile155Ile	synonymous	Exon 3 of 4	NP_619527.1
	BCL2L11	NM_001204108.1		c.465T>C	p.Ile155Ile	synonymous	Exon 3 of 5	NP_001191037.1
	BCL2L11	NM_138622.4		c.465T>C	p.Ile155Ile	synonymous	Exon 3 of 5	NP_619528.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	ENST00000393256.8	TSL:1 MANE Select	c.465T>C	p.Ile155Ile	synonymous	Exon 3 of 4	ENSP00000376943.2
	BCL2L11	ENST00000361493.10	TSL:1	n.*83T>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000354879.6
	BCL2L11	ENST00000437029.5	TSL:1	n.465T>C		non_coding_transcript_exon	Exon 2 of 4	ENSP00000412892.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105275 AN: 152044 Hom.: 37062 Cov.: 33

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.660

GnomAD2 exomes AF: 0.644 AC: 161732 AN: 251064 AF XY: 0.641

Gnomad AFR exome AF: 0.796

Gnomad AMR exome AF: 0.436

Gnomad ASJ exome AF: 0.613

Gnomad EAS exome AF: 0.873

Gnomad FIN exome AF: 0.652

Gnomad NFE exome AF: 0.677

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.674 AC: 985623 AN: 1461320 Hom.: 336549 Cov.: 55 AF XY: 0.671 AC XY: 487464 AN XY: 726946

African (AFR) AF: 0.795 AC: 26592 AN: 33466

American (AMR) AF: 0.449 AC: 20074 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 15972 AN: 26120

East Asian (EAS) AF: 0.899 AC: 35665 AN: 39674

South Asian (SAS) AF: 0.546 AC: 47115 AN: 86244

European-Finnish (FIN) AF: 0.658 AC: 35087 AN: 53332

Middle Eastern (MID) AF: 0.529 AC: 3052 AN: 5764

European-Non Finnish (NFE) AF: 0.685 AC: 761672 AN: 1111666

Other (OTH) AF: 0.669 AC: 40394 AN: 60354

GnomAD4 genome AF: 0.692 AC: 105347 AN: 152162 Hom.: 37091 Cov.: 33 AF XY: 0.687 AC XY: 51069 AN XY: 74374

African (AFR) AF: 0.788 AC: 32697 AN: 41518

American (AMR) AF: 0.544 AC: 8322 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3470

East Asian (EAS) AF: 0.861 AC: 4463 AN: 5186

South Asian (SAS) AF: 0.554 AC: 2672 AN: 4826

European-Finnish (FIN) AF: 0.659 AC: 6976 AN: 10584

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45943 AN: 67970

Other (OTH) AF: 0.661 AC: 1392 AN: 2106

Alfa AF: 0.677 Hom.: 128518

Bravo AF: 0.691

Asia WGS AF: 0.685 AC: 2384 AN: 3478

EpiCase AF: 0.660

EpiControl AF: 0.658

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs724710; hg19: chr2-111907691; COSMIC: COSV58033046; COSMIC: COSV58033046;