2-111153474-A-T

Variant names:

• chr2-111153474-A-T
• rs3827537
• NM_138621.5:c.498+3327A>T

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+3327A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 152,306 control chromosomes in the GnomAD database, including 44 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 0.0044 (44 hom., cov: 32)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 1 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 = 0.106 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	NM_138621.5	MANE Select	c.498+3327A>T		intron	N/A	NP_619527.1
	BCL2L11	NM_001204108.1		c.498+3327A>T		intron	N/A	NP_001191037.1
	BCL2L11	NM_138622.4		c.499-306A>T		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+3327A>T		intron	N/A	ENSP00000376943.2
	BCL2L11	ENST00000361493.10	TSL:1	n.*116+3327A>T		intron	N/A	ENSP00000354879.6
	BCL2L11	ENST00000415458.5	TSL:1	n.215-306A>T		intron	N/A	ENSP00000393781.1

Frequencies

GnomAD3 genomes AF: 0.00436 AC: 663 AN: 152188 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00382

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

GnomAD4 genome AF: 0.00435 AC: 663 AN: 152306 Hom.: 44 Cov.: 32 AF XY: 0.00481 AC XY: 358 AN XY: 74462

African (AFR) AF: 0.0000722 AC: 3 AN: 41568

American (AMR) AF: 0.00137 AC: 21 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.113 AC: 588 AN: 5184

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4820

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68020

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.000797 Hom.: 0

Bravo AF: 0.00428

Asia WGS AF: 0.0550 AC: 191 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	6.3
DANN	Benign	0.85
PhyloP100		0.21
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: rs3827537; hg19: chr2-111911051;