Genetic Variant GPBAR1:c.-176C>T (chr2-218261086-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.-176C>T 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 152,188 control chromosomes in the GnomAD database, including 17,945 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 ( 17923 hom., cov: 33)

Exomes 𝑓: 0.62 ( 22 hom. )

Consequence

GPBAR1
NM_170699.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.567

Publications

43 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170699.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GPBAR1	NM_170699.3	MANE Select	c.-176C>T	5_prime_UTR	Exon 1 of 2	NP_733800.1	Q8TDU6
GPBAR1	NM_001077191.2		c.-797C>T	5_prime_UTR	Exon 1 of 2	NP_001070659.1	Q8TDU6
GPBAR1	NM_001077194.2		c.-289C>T	5_prime_UTR	Exon 1 of 2	NP_001070662.1	Q8TDU6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GPBAR1	ENST00000519574.2	TSL:1 MANE Select	c.-176C>T	5_prime_UTR	Exon 1 of 2	ENSP00000430202.1	Q8TDU6
GPBAR1	ENST00000521462.1	TSL:2	c.-289C>T	5_prime_UTR	Exon 1 of 2	ENSP00000428824.1	Q8TDU6
GPBAR1	ENST00000522678.5	TSL:2	c.-797C>T	5_prime_UTR	Exon 1 of 2	ENSP00000430886.1	Q8TDU6

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68258

AN:

151966

Hom.:

17900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.625

Gnomad FIN

AF:

0.688

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.443

GnomAD4 exome

AF:

0.618

AC:

AN:

102

Hom.:

Cov.:

AF XY:

0.618

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.628

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

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:

0.449

AC:

68304

AN:

152086

Hom.:

17923

Cov.:

AF XY:

0.455

AC XY:

33865

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.163

AC:

6781

AN:

41488

American (AMR)

AF:

0.474

AC:

7255

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

1701

AN:

3468

East Asian (EAS)

AF:

0.565

AC:

2912

AN:

5150

South Asian (SAS)

AF:

0.625

AC:

3017

AN:

4830

European-Finnish (FIN)

AF:

0.688

AC:

7293

AN:

10600

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.558

AC:

37912

AN:

67940

Other (OTH)

AF:

0.446

AC:

943

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1745

3490

5235

6980

8725

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:

0.511

Hom.:

32109

Bravo

AF:

0.419

Asia WGS

AF:

0.605

AC:

2105

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.7

(source)

DANN

Benign

0.61

PhyloP100

-0.57

PromoterAI

0.054

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over