2-218262879-GCTT-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2

The NM_170699.3(GPBAR1):​c.160_162del​(p.Phe54del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000211 in 1,613,522 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (β˜…).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

GPBAR1
NM_170699.3 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_170699.3. Strenght limited to Supporting due to length of the change: 1aa.
BP6
Variant 2-218262879-GCTT-G is Benign according to our data. Variant chr2-218262879-GCTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 500565.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPBAR1NM_170699.3 linkuse as main transcriptc.160_162del p.Phe54del inframe_deletion 2/2 ENST00000519574.2 NP_733800.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPBAR1ENST00000519574.2 linkuse as main transcriptc.160_162del p.Phe54del inframe_deletion 2/21 NM_170699.3 ENSP00000430202 P1
GPBAR1ENST00000479077.5 linkuse as main transcriptc.160_162del p.Phe54del inframe_deletion 2/22 ENSP00000430698 P1
GPBAR1ENST00000521462.1 linkuse as main transcriptc.160_162del p.Phe54del inframe_deletion 2/22 ENSP00000428824 P1
GPBAR1ENST00000522678.5 linkuse as main transcriptc.160_162del p.Phe54del inframe_deletion 2/22 ENSP00000430886 P1

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00113
AC:
279
AN:
247612
Hom.:
1
AF XY:
0.000788
AC XY:
106
AN XY:
134496
show subpopulations
Gnomad AFR exome
AF:
0.000131
Gnomad AMR exome
AF:
0.00788
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.000665
GnomAD4 exome
AF:
0.000214
AC:
312
AN:
1461316
Hom.:
2
AF XY:
0.000166
AC XY:
121
AN XY:
726942
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00665
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000477
Hom.:
0
Bravo
AF:
0.000559
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Feb 23, 2017- -
GPBAR1-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesSep 19, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs767819043; hg19: chr2-219127602; API