NM_138621.5:c.395-7023A>G

Variant names:

• chr2-111143021-A-G
• rs13396983
• NM_138621.5:c.395-7023A>G

Variant summary

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

The NM_138621.5(BCL2L11):​c.395-7023A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,072 control chromosomes in the GnomAD database, including 22,931 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 0.54 (22931 hom., cov: 32)
• Consequence: BCL2L11 NM_138621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 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.395-7023A>G		intron	N/A	NP_619527.1
	BCL2L11	NM_001204108.1		c.395-7023A>G		intron	N/A	NP_001191037.1
	BCL2L11	NM_138622.4		c.395-7023A>G		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.395-7023A>G		intron	N/A	ENSP00000376943.2
	BCL2L11	ENST00000361493.10	TSL:1	n.*13-7023A>G		intron	N/A	ENSP00000354879.6
	BCL2L11	ENST00000415458.5	TSL:1	n.215-10759A>G		intron	N/A	ENSP00000393781.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82179 AN: 151954 Hom.: 22902 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.541 AC: 82255 AN: 152072 Hom.: 22931 Cov.: 32 AF XY: 0.534 AC XY: 39685 AN XY: 74324

African (AFR) AF: 0.641 AC: 26587 AN: 41476

American (AMR) AF: 0.394 AC: 6016 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1417 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2867 AN: 5176

South Asian (SAS) AF: 0.319 AC: 1543 AN: 4830

European-Finnish (FIN) AF: 0.527 AC: 5562 AN: 10556

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36599 AN: 67966

Other (OTH) AF: 0.500 AC: 1058 AN: 2114

Alfa AF: 0.523 Hom.: 12410

Bravo AF: 0.540

Asia WGS AF: 0.420 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.5
DANN	Benign	0.55
PhyloP100		-0.0070
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: rs13396983; hg19: chr2-111900598;