rs112446582

Variant names:

• chr2-111123784-C-G
• rs112446582
• NM_138621.5:c.39C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-111123784-C-G
• chr2-111123784-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_138621.5(BCL2L11):​c.39C>G​(p.Asp13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000849 in 1,296,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D13D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: BCL2L11 NM_138621.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30110508).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L11	NM_138621.5	c.39C>G	p.Asp13Glu	missense_variant	Exon 2 of 4	ENST00000393256.8	NP_619527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8	c.39C>G	p.Asp13Glu	missense_variant	Exon 2 of 4	1	NM_138621.5	ENSP00000376943.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000849 AC: 11 AN: 1296350 Hom.: 0 Cov.: 32 AF XY: 0.0000143 AC XY: 9 AN XY: 630986

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	.;.;T;.;.;.;.;.;.;.;.;D;T;.;.;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.84	T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.30	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.69	.;N;.;N;N;N;N;N;N;N;N;N;.;N;N;N;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.7	D;D;D;D;.;.;.;.;.;.;.;D;D;D;.;.;D
REVEL	Benign	0.067
Sift	Uncertain	0.0060	D;D;D;D;.;.;.;.;.;.;.;D;D;D;.;.;D
Sift4G	Uncertain	0.014	D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;.;D
Polyphen		0.093, 1.0, 0.0010, 0.0030	.;B;.;D;.;.;.;B;.;.;.;B;.;B;.;.;.
Vest4		0.29, 0.26, 0.24, 0.28, 0.34, 0.35, 0.28, 0.28, 0.28, 0.25, 0.29, 0.30
MutPred		0.42		Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);.;
MVP		0.30
MPC		0.059
ClinPred		0.96	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.072

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: rs112446582; hg19: chr2-111881361;