2-111146121-A-G

Variant names:

• chr2-111146121-A-G
• rs3761704
• NM_138621.5:c.395-3923A>G

Variant summary

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

The NM_001204113.1(BCL2L11):​c.*202A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 984,766 control chromosomes in the GnomAD database, including 8,405 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 0.11 (1039 hom., cov: 30)
  • Exomes 𝑓: 0.13 (7366 hom.)
• Consequence: BCL2L11 NM_001204113.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.967
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204113.1. 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.395-3923A>G		intron	N/A	NP_619527.1	O43521-1
	BCL2L11	NM_001204113.1		c.*202A>G		3_prime_UTR	Exon 6 of 6	NP_001191042.1	H7BZE5
	BCL2L11	NM_001204108.1		c.395-3923A>G		intron	N/A	NP_001191037.1	O43521-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	ENST00000393256.8	TSL:1 MANE Select	c.395-3923A>G		intron	N/A	ENSP00000376943.2	O43521-1
	BCL2L11	ENST00000361493.10	TSL:1	n.*13-3923A>G		intron	N/A	ENSP00000354879.6	A0A0C4DH20
	BCL2L11	ENST00000415458.5	TSL:1	n.215-7659A>G		intron	N/A	ENSP00000393781.1	O43521-16

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17117 AN: 151926 Hom.: 1035 Cov.: 30

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0879

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0972

GnomAD4 exome AF: 0.132 AC: 109834 AN: 832722 Hom.: 7366 Cov.: 32 AF XY: 0.132 AC XY: 50654 AN XY: 384536

African (AFR) AF: 0.0968 AC: 1527 AN: 15782

American (AMR) AF: 0.0783 AC: 77 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0538 AC: 277 AN: 5152

East Asian (EAS) AF: 0.268 AC: 971 AN: 3626

South Asian (SAS) AF: 0.0814 AC: 1339 AN: 16458

European-Finnish (FIN) AF: 0.0797 AC: 22 AN: 276

Middle Eastern (MID) AF: 0.0630 AC: 102 AN: 1620

European-Non Finnish (NFE) AF: 0.134 AC: 102063 AN: 761538

Other (OTH) AF: 0.127 AC: 3456 AN: 27286

GnomAD4 genome AF: 0.113 AC: 17138 AN: 152044 Hom.: 1039 Cov.: 30 AF XY: 0.109 AC XY: 8113 AN XY: 74348

African (AFR) AF: 0.105 AC: 4346 AN: 41482

American (AMR) AF: 0.0879 AC: 1342 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1342 AN: 5162

South Asian (SAS) AF: 0.0785 AC: 378 AN: 4816

European-Finnish (FIN) AF: 0.0836 AC: 883 AN: 10556

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8293 AN: 67984

Other (OTH) AF: 0.102 AC: 216 AN: 2110

Alfa AF: 0.119 Hom.: 492

Bravo AF: 0.116

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.80
PhyloP100		0.97
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: rs3761704; hg19: chr2-111903698;