2-111158369-G-T

Variant names:

• chr2-111158369-G-T
• rs1470053
• NM_138621.5:c.499-5764G>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.499-5764G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,974 control chromosomes in the GnomAD database, including 1,737 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 0.13 (1737 hom., cov: 32)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 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.499-5764G>T		intron	N/A	NP_619527.1
	BCL2L11	NM_001204108.1		c.499-3050G>T		intron	N/A	NP_001191037.1
	BCL2L11	NM_138622.4		c.*113+4465G>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.499-5764G>T		intron	N/A	ENSP00000376943.2
	BCL2L11	ENST00000361493.10	TSL:1	n.*117-5764G>T		intron	N/A	ENSP00000354879.6
	BCL2L11	ENST00000415458.5	TSL:1	n.*96+4465G>T		intron	N/A	ENSP00000393781.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20383 AN: 151858 Hom.: 1739 Cov.: 32

Gnomad AFR AF: 0.0337

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.134 AC: 20372 AN: 151974 Hom.: 1737 Cov.: 32 AF XY: 0.137 AC XY: 10154 AN XY: 74264

African (AFR) AF: 0.0335 AC: 1391 AN: 41474

American (AMR) AF: 0.109 AC: 1667 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3470

East Asian (EAS) AF: 0.170 AC: 880 AN: 5164

South Asian (SAS) AF: 0.126 AC: 603 AN: 4802

European-Finnish (FIN) AF: 0.234 AC: 2468 AN: 10532

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.179 AC: 12151 AN: 67950

Other (OTH) AF: 0.145 AC: 305 AN: 2108

Alfa AF: 0.152 Hom.: 3794

Bravo AF: 0.122

Asia WGS AF: 0.119 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.50
DANN	Benign	0.49
PhyloP100		-0.22
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: rs1470053; hg19: chr2-111915946;