2-111146121-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L11	NM_138621.5	c.395-3923A>G		intron_variant	Intron 2 of 3	ENST00000393256.8	NP_619527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8	c.395-3923A>G		intron_variant	Intron 2 of 3	1	NM_138621.5	ENSP00000376943.2

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

Gnomad4 AFR exome AF: 0.0968

Gnomad4 AMR exome AF: 0.0783

Gnomad4 ASJ exome AF: 0.0538

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.0814

Gnomad4 FIN exome AF: 0.0797

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.127

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

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.0785

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.102

Alfa AF: 0.114 Hom.: 248

Bravo AF: 0.116

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs3761704; hg19: chr2-111903698; COSMIC: COSV105892679;