Genetic Variant BAD:c.187+2742G>A (chr11-64281440-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032989.3(BAD):c.187+2742G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,156 control chromosomes in the GnomAD database, including 43,447 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 0.74 ( 43447 hom., cov: 33)

Consequence

BAD
NM_032989.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.417

Publications

39 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
BAD	NM_032989.3	MANE Select	c.187+2742G>A	intron	N/A	NP_116784.1	Q92934
GPR137	NM_001378078.1		c.-15-5070C>T	intron	N/A	NP_001365007.1	Q96N19-2
GPR137	NM_001378076.1		c.-15-5070C>T	intron	N/A	NP_001365005.1	Q96N19-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BAD	ENST00000309032.8	TSL:1 MANE Select	c.187+2742G>A	intron	N/A	ENSP00000309103.3	Q92934
GPR137	ENST00000546139.5	TSL:1	c.4-5070C>T	intron	N/A	ENSP00000445570.1	F5H234
BAD	ENST00000394532.7	TSL:1	c.187+2742G>A	intron	N/A	ENSP00000378040.3	Q92934

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112585

AN:

152038

Hom.:

43431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.894

Gnomad AMR

AF:

0.810

Gnomad ASJ

AF:

0.884

Gnomad EAS

AF:

0.817

Gnomad SAS

AF:

0.756

Gnomad FIN

AF:

0.834

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.751

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

GnomAD4 genome

AF:

0.740

AC:

112643

AN:

152156

Hom.:

43447

Cov.:

AF XY:

0.743

AC XY:

55264

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.502

AC:

20809

AN:

41466

American (AMR)

AF:

0.810

AC:

12383

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.884

AC:

3069

AN:

3472

East Asian (EAS)

AF:

0.818

AC:

4231

AN:

5174

South Asian (SAS)

AF:

0.757

AC:

3657

AN:

4828

European-Finnish (FIN)

AF:

0.834

AC:

8845

AN:

10608

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.838

AC:

57019

AN:

68012

Other (OTH)

AF:

0.746

AC:

1576

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1334

2668

4002

5336

6670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<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:

0.806

Hom.:

139808

Bravo

AF:

0.732

Asia WGS

AF:

0.757

AC:

2634

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.3

(source)

DANN

Benign

0.75

PhyloP100

0.42

Mutation Taster

=100/0

polymorphism (auto)

(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