Genetic Variant GPBAR1:c.-731G>A (chr2-218259499-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001321950.2(GPBAR1):c.-731G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,350 control chromosomes in the GnomAD database, including 17,952 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 0.45 ( 17905 hom., cov: 32)

Exomes 𝑓: 0.58 ( 47 hom. )

Consequence

GPBAR1
NM_001321950.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.79

Publications

20 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBAR1	NM_001321950.2 link	c.-731G>A		5_prime_UTR_variant	Exon 1 of 2		NP_001308879.1	Q8TDU6
GPBAR1	XM_011510743.1 link	c.-1352G>A		5_prime_UTR_variant	Exon 1 of 2		XP_011509045.1	Q8TDU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPBAR1	ENST00000479077.5 link	c.-731G>A		5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000430698.1		Q8TDU6

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68229

AN:

151966

Hom.:

17882

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.443

GnomAD4 exome

AF:

0.576

AC:

152

AN:

264

Hom.:

Cov.:

AF XY:

0.544

AC XY:

AN XY:

180

show subpopulations

African (AFR)

AF:

0.200

AC:

AN:

American (AMR)

AF:

0.400

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.625

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.708

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.596

AC:

106

AN:

178

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.449

AC:

68276

AN:

152086

Hom.:

17905

Cov.:

AF XY:

0.455

AC XY:

33848

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.164

AC:

6792

AN:

41502

American (AMR)

AF:

0.473

AC:

7236

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

1702

AN:

3468

East Asian (EAS)

AF:

0.566

AC:

2925

AN:

5164

South Asian (SAS)

AF:

0.624

AC:

3008

AN:

4820

European-Finnish (FIN)

AF:

0.689

AC:

7282

AN:

10576

Middle Eastern (MID)

AF:

0.387

AC:

113

AN:

292

European-Non Finnish (NFE)

AF:

0.558

AC:

37900

AN:

67962

Other (OTH)

AF:

0.446

AC:

942

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1727

3454

5181

6908

8635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.513

Hom.:

26515

Bravo

AF:

0.418

Asia WGS

AF:

0.605

AC:

2104

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.023

(source)

DANN

Benign

0.78

PhyloP100

-4.8

PromoterAI

0.040

Neutral

(source)

Mutation Taster

=300/0

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