chr11-64270315-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_032989.3(BAD):c.401G>C(p.Ser134Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000636 in 1,414,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

BAD
NM_032989.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity BAD_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2752059).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAD	NM_032989.3	MANE Select	c.401G>C	p.Ser134Thr	missense	Exon 4 of 4	NP_116784.1	Q92934
BAD	NM_004322.3		c.401G>C	p.Ser134Thr	missense	Exon 3 of 3	NP_004313.1	Q92934
GPR137	NM_001378078.1		c.-362C>G		upstream_gene	N/A	NP_001365007.1	Q96N19-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAD	ENST00000309032.8	TSL:1 MANE Select	c.401G>C	p.Ser134Thr	missense	Exon 4 of 4	ENSP00000309103.3	Q92934
BAD	ENST00000394532.7	TSL:1	c.401G>C	p.Ser134Thr	missense	Exon 3 of 3	ENSP00000378040.3	Q92934
GPR137	ENST00000546139.5	TSL:1	c.-344C>G		5_prime_UTR	Exon 1 of 5	ENSP00000445570.1	F5H234

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000896

AC:

AN:

223120

AF XY:

0.00000832

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000196

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000636

AC:

AN:

1414868

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

697180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32322

American (AMR)

AF:

0.00

AC:

AN:

39672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23420

East Asian (EAS)

AF:

0.00

AC:

AN:

38958

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51966

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5538

European-Non Finnish (NFE)

AF:

0.00000462

AC:

AN:

1083100

Other (OTH)

AF:

0.0000344

AC:

AN:

58214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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

Cov.:

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

0.32

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.48

PhyloP100

3.9

PROVEAN

Benign

-0.020

REVEL

Benign

0.074

Sift

Benign

0.17

Sift4G

Benign

0.36

Vest4

0.27

MutPred

0.26

Loss of helix (P = 0.0558)

MVP

0.38

ClinPred

0.97

GERP RS

5.7

PromoterAI

0.050

Neutral

(source)

Varity_R

0.74

Mutation Taster

=80/20

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over