11-64270237-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032989.3(BAD):c.479G>T(p.Gly160Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,612,206 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G160R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

BAD
NM_032989.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Publications

0 publications found

Variant links:

Genes affected

BAD (HGNC:936): (BCL2 associated agonist of cell death) The protein encoded by this gene is a member of the BCL-2 family. BCL-2 family members are known to be regulators of programmed cell death. This protein positively regulates cell apoptosis by forming heterodimers with BCL-xL (B-cell lymphoma-extra large) and BCL-2, and reversing their death repressor activity. Proapoptotic activity of this protein is regulated through its phosphorylation. Protein kinases AKT and MAP kinase, as well as protein phosphatase calcineurin were found to be involved in the regulation of this protein. Alternative splicing of this gene results in two transcript variants which encode the same isoform. [provided by RefSeq, Dec 2019]

BAD links:

GPR137 (HGNC:24300): (G protein-coupled receptor 137) Predicted to be involved in several processes, including negative regulation of bone resorption; negative regulation of osteoclast differentiation; and positive regulation of TORC1 signaling. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR137 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032989.3. 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
	BAD	NM_032989.3	MANE Select	c.479G>T	p.Gly160Val	missense	Exon 4 of 4	NP_116784.1	Q92934
	BAD	NM_004322.3		c.479G>T	p.Gly160Val	missense	Exon 3 of 3	NP_004313.1	Q92934

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAD	ENST00000309032.8	TSL:1 MANE Select	c.479G>T	p.Gly160Val	missense	Exon 4 of 4	ENSP00000309103.3	Q92934
BAD	ENST00000394532.7	TSL:1	c.479G>T	p.Gly160Val	missense	Exon 3 of 3	ENSP00000378040.3	Q92934
GPR137	ENST00000546139.5	TSL:1	c.-422C>A		5_prime_UTR	Exon 1 of 5	ENSP00000445570.1	F5H234

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250136

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1459950

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1110720

Other (OTH)

AF:

0.0000166

AC:

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.79

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.8

PhyloP100

1.7

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.25

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.51

MutPred

0.66

Loss of methylation at R161 (P = 0.0522)

MVP

0.90

MPC

1.2

ClinPred

0.99

GERP RS

5.2

PromoterAI

0.026

Neutral

(source)

Varity_R

0.72

gMVP

0.051

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over