chr2-218262736-C-T

Variant names:

• chr2-218262736-C-T
• rs202233050
• NM_170699.3:c.12C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_170699.3(GPBAR1):​c.12C>T​(p.Asn4Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,591,254 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: GPBAR1 NM_170699.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 2-218262736-C-T is Benign according to our data. Variant chr2-218262736-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3358501.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBAR1	NM_170699.3	MANE Select	c.12C>T	p.Asn4Asn	synonymous	Exon 2 of 2	NP_733800.1	Q8TDU6
	GPBAR1	NM_001077191.2		c.12C>T	p.Asn4Asn	synonymous	Exon 2 of 2	NP_001070659.1	Q8TDU6
	GPBAR1	NM_001077194.2		c.12C>T	p.Asn4Asn	synonymous	Exon 2 of 2	NP_001070662.1	Q8TDU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBAR1	ENST00000519574.2	TSL:1 MANE Select	c.12C>T	p.Asn4Asn	synonymous	Exon 2 of 2	ENSP00000430202.1	Q8TDU6
	GPBAR1	ENST00000479077.5	TSL:2	c.12C>T	p.Asn4Asn	synonymous	Exon 2 of 2	ENSP00000430698.1	Q8TDU6
	GPBAR1	ENST00000521462.1	TSL:2	c.12C>T	p.Asn4Asn	synonymous	Exon 2 of 2	ENSP00000428824.1	Q8TDU6

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152128 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000277 AC: 64 AN: 231264 AF XY: 0.000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00604

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000666

Gnomad OTH exome AF: 0.000534

GnomAD4 exome AF: 0.000155 AC: 223 AN: 1439126 Hom.: 1 Cov.: 31 AF XY: 0.000160 AC XY: 114 AN XY: 712916

African (AFR) AF: 0.00 AC: 0 AN: 33124

American (AMR) AF: 0.00 AC: 0 AN: 43530

Ashkenazi Jewish (ASJ) AF: 0.00645 AC: 162 AN: 25126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39194

South Asian (SAS) AF: 0.00 AC: 0 AN: 84282

European-Finnish (FIN) AF: 0.0000201 AC: 1 AN: 49716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000382 AC: 42 AN: 1099060

Other (OTH) AF: 0.000303 AC: 18 AN: 59396

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152128 Hom.: 1 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74296

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000637 Hom.: 0

Bravo AF: 0.000166

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GPBAR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.5
DANN	Benign	0.56
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs202233050; hg19: chr2-219127459;