rs61733244

Variant names:

• chr12-12079349-A-G
• rs61733244
• NM_138723.2:c.44A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138723.2(BCL2L14):​c.44A>G​(p.Asp15Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000805 in 1,614,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: BCL2L14 NM_138723.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• Publications: 1 publications found

Genes affected

BCL2L14 (HGNC:16657): (BCL2 like 14) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Overexpression of this gene has been shown to induce apoptosis in cells. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported for this gene. [provided by RefSeq, May 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033307344).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138723.2. 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
	BCL2L14	NM_138723.2	MANE Select	c.44A>G	p.Asp15Gly	missense	Exon 2 of 6	NP_620049.1	Q9BZR8-1
	BCL2L14	NM_001370268.1		c.44A>G	p.Asp15Gly	missense	Exon 3 of 7	NP_001357197.1	Q9BZR8-1
	BCL2L14	NM_001370269.1		c.44A>G	p.Asp15Gly	missense	Exon 4 of 8	NP_001357198.1	Q9BZR8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L14	ENST00000308721.9	TSL:1 MANE Select	c.44A>G	p.Asp15Gly	missense	Exon 2 of 6	ENSP00000309132.4	Q9BZR8-1
	BCL2L14	ENST00000396367.5	TSL:1	c.44A>G	p.Asp15Gly	missense	Exon 2 of 6	ENSP00000379653.1	Q9BZR8-1
	BCL2L14	ENST00000266434.8	TSL:1	c.44A>G	p.Asp15Gly	missense	Exon 2 of 6	ENSP00000266434.4	Q9BZR8-2

Frequencies

GnomAD3 genomes AF: 0.000420 AC: 64 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000111 AC: 28 AN: 251374 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000451 AC: 66 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 727214

African (AFR) AF: 0.00155 AC: 52 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.000420 AC: 64 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.000456 AC XY: 34 AN XY: 74484

African (AFR) AF: 0.00152 AC: 63 AN: 41578

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000225 Hom.: 0

Bravo AF: 0.000510

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000123 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.069	T
Eigen	Benign	0.058
Eigen_PC	Benign	-0.025
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.9
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.080
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.95	P
Vest4		0.28
MVP		0.78
MPC		0.52
ClinPred		0.15	T
GERP RS		2.9
PromoterAI		-0.013	Neutral
Varity_R		0.19
gMVP		0.17
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs61733244; hg19: chr12-12232283; COSMIC: COSV99844996;