2-111166053-T-G

Variant names:

• chr2-111166053-T-G
• rs6753785
• NM_138621.5:c.*1822T>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.*1822T>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 0.552 in 152,420 control chromosomes in the GnomAD database, including 23,920 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 0.55 (23861 hom., cov: 32)
  • Exomes 𝑓: 0.54 (59 hom.)
• Consequence: BCL2L11 NM_138621.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 14 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	NM_138621.5	MANE Select	c.*1822T>G		3_prime_UTR	Exon 4 of 4	NP_619527.1	O43521-1
	BCL2L11	NM_001204108.1		c.*2032T>G		3_prime_UTR	Exon 5 of 5	NP_001191037.1	O43521-8
	BCL2L11	NM_138622.4		c.*2034T>G		3_prime_UTR	Exon 5 of 5	NP_619528.1	O43521-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	ENST00000393256.8	TSL:1 MANE Select	c.*1822T>G		3_prime_UTR	Exon 4 of 4	ENSP00000376943.2	O43521-1
	BCL2L11	ENST00000393252.4	TSL:2	c.*1822T>G		3_prime_UTR	Exon 4 of 4	ENSP00000376941.4	E9PAM9
	BCL2L11	ENST00000715206.1		c.*1822T>G		3_prime_UTR	Exon 4 of 4	ENSP00000520413.1	O43521-1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83767 AN: 151876 Hom.: 23832 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.535 AC: 228 AN: 426 Hom.: 59 Cov.: 0 AF XY: 0.558 AC XY: 145 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.533 AC: 223 AN: 418

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.552 AC: 83844 AN: 151994 Hom.: 23861 Cov.: 32 AF XY: 0.544 AC XY: 40410 AN XY: 74266

African (AFR) AF: 0.657 AC: 27246 AN: 41454

American (AMR) AF: 0.404 AC: 6179 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1450 AN: 3470

East Asian (EAS) AF: 0.561 AC: 2890 AN: 5156

South Asian (SAS) AF: 0.320 AC: 1545 AN: 4826

European-Finnish (FIN) AF: 0.537 AC: 5665 AN: 10542

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37170 AN: 67952

Other (OTH) AF: 0.516 AC: 1090 AN: 2112

Alfa AF: 0.482 Hom.: 1897

Bravo AF: 0.552

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.64
PhyloP100		0.15
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: rs6753785; hg19: chr2-111923630;