Genetic Variant NM_170699.3:c.-39C>T (chr2-218262686-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.-39C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,506,832 control chromosomes in the GnomAD database, including 245 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 0.023 ( 111 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 134 hom. )

Consequence

GPBAR1
NM_170699.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

Publications

2 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:

Genome browser will be placed here

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 (AFR) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBAR1	NM_170699.3 link	c.-39C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 2	ENST00000519574.2	NP_733800.1	Q8TDU6
GPBAR1	NM_170699.3 link	c.-39C>T		5_prime_UTR_variant	Exon 2 of 2	ENST00000519574.2	NP_733800.1	Q8TDU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPBAR1	ENST00000519574.2 link	c.-39C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1		Q8TDU6
GPBAR1	ENST00000519574.2 link	c.-39C>T		5_prime_UTR_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1		Q8TDU6

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3507

AN:

152116

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0784

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00968

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.00656

AC:

963

AN:

146828

AF XY:

0.00532

show subpopulations

Gnomad AFR exome

AF:

0.0780

Gnomad AMR exome

AF:

0.00405

Gnomad ASJ exome

AF:

0.00470

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000572

Gnomad OTH exome

AF:

0.00450

GnomAD4 exome

AF:

0.00275

AC:

3727

AN:

1354598

Hom.:

134

Cov.:

AF XY:

0.00244

AC XY:

1618

AN XY:

662960

show subpopulations

African (AFR)

AF:

0.0861

AC:

2670

AN:

31018

American (AMR)

AF:

0.00452

AC:

151

AN:

33428

Ashkenazi Jewish (ASJ)

AF:

0.00557

AC:

118

AN:

21198

East Asian (EAS)

AF:

0.0000268

AC:

AN:

37304

South Asian (SAS)

AF:

0.000238

AC:

AN:

71578

European-Finnish (FIN)

AF:

0.0000556

AC:

AN:

35958

Middle Eastern (MID)

AF:

0.00565

AC:

AN:

5132

European-Non Finnish (NFE)

AF:

0.000334

AC:

355

AN:

1062794

Other (OTH)

AF:

0.00683

AC:

384

AN:

56188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

165

329

494

658

823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.0231

AC:

3518

AN:

152234

Hom.:

111

Cov.:

AF XY:

0.0222

AC XY:

1654

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0785

AC:

3258

AN:

41522

American (AMR)

AF:

0.00967

AC:

148

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68014

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

166

332

499

665

831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0137

Hom.:

Bravo

AF:

0.0271

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.3

(source)

DANN

Benign

0.73

PhyloP100

-1.9

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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