Genetic Variant GPBAR1:c.*66C>T (chr2-218263783-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_170699.3(GPBAR1):c.*66C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 1,591,806 control chromosomes in the GnomAD database, including 710,341 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 0.81 ( 54079 hom., cov: 33)

Exomes 𝑓: 0.95 ( 656262 hom. )

Consequence

GPBAR1
NM_170699.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.563

Publications

15 publications found

Variant links:

Genes affected

GPBAR1 (HGNC:19680): (G protein-coupled bile acid receptor 1) This gene encodes a member of the G protein-coupled receptor (GPCR) superfamily. This enzyme functions as a cell surface receptor for bile acids. Treatment of cells expressing this GPCR with bile acids induces the production of intracellular cAMP, activation of a MAP kinase signaling pathway, and internalization of the receptor. The receptor is implicated in the suppression of macrophage functions and regulation of energy homeostasis by bile acids. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

GPBAR1 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBAR1	NM_170699.3 link	c.*66C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000519574.2	NP_733800.1	Q8TDU6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPBAR1	ENST00000519574.2 link	c.*66C>T	3_prime_UTR_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1	Q8TDU6
GPBAR1	ENST00000479077.5 link	c.*66C>T	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000430698.1	Q8TDU6
GPBAR1	ENST00000521462.1 link	c.*66C>T	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000428824.1	Q8TDU6
GPBAR1	ENST00000522678.5 link	c.*66C>T	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000430886.1	Q8TDU6

Frequencies

GnomAD3 genomes

AF:

0.807

AC:

122823

AN:

152108

Hom.:

54066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.962

Gnomad AMR

AF:

0.907

Gnomad ASJ

AF:

0.906

Gnomad EAS

AF:

0.991

Gnomad SAS

AF:

0.974

Gnomad FIN

AF:

0.974

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.963

Gnomad OTH

AF:

0.836

GnomAD4 exome

AF:

0.951

AC:

1368598

AN:

1439580

Hom.:

656262

Cov.:

AF XY:

0.953

AC XY:

683686

AN XY:

717530

show subpopulations

African (AFR)

AF:

0.393

AC:

12967

AN:

32988

American (AMR)

AF:

0.941

AC:

42036

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.913

AC:

23736

AN:

25994

East Asian (EAS)

AF:

0.989

AC:

39146

AN:

39562

South Asian (SAS)

AF:

0.974

AC:

83595

AN:

85844

European-Finnish (FIN)

AF:

0.977

AC:

51071

AN:

52288

Middle Eastern (MID)

AF:

0.901

AC:

5159

AN:

5724

European-Non Finnish (NFE)

AF:

0.966

AC:

1055539

AN:

1092854

Other (OTH)

AF:

0.928

AC:

55349

AN:

59670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3173

6346

9518

12691

15864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21022

42044

63066

84088

105110

<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:

0.807

AC:

122866

AN:

152226

Hom.:

54079

Cov.:

AF XY:

0.811

AC XY:

60380

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.417

AC:

17280

AN:

41484

American (AMR)

AF:

0.907

AC:

13885

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.906

AC:

3145

AN:

3472

East Asian (EAS)

AF:

0.991

AC:

5141

AN:

5186

South Asian (SAS)

AF:

0.974

AC:

4700

AN:

4824

European-Finnish (FIN)

AF:

0.974

AC:

10341

AN:

10622

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.963

AC:

65467

AN:

68016

Other (OTH)

AF:

0.839

AC:

1771

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

779

1558

2338

3117

3896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.903

Hom.:

173874

Bravo

AF:

0.784

Asia WGS

AF:

0.935

AC:

3251

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.056

(source)

DANN

Benign

0.75

PhyloP100

-0.56

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over