1-6574673-C-G

Position:

chr1-6574673-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_138697.4(TAS1R1):c.541C>G(p.Gln181Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,264 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 6 hom. )

Consequence

TAS1R1
NM_138697.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.49

Variant links:

Genes affected

TAS1R1 (HGNC:14448): (taste 1 receptor member 1) The protein encoded by this gene is a G protein-coupled receptor and is a component of the heterodimeric amino acid taste receptor T1R1+3. The T1R1+3 receptor responds to L-amino acids but not to D-enantiomers or other compounds. Most amino acids that are perceived as sweet activate T1R1+3, and this activation is strictly dependent on an intact T1R1+3 heterodimer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

TAS1R1 links:

LOC107984912 (HGNC:):

LOC107984912 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011758864).

BP6

Variant 1-6574673-C-G is Benign according to our data. Variant chr1-6574673-C-G is described in ClinVar as [Benign]. Clinvar id is 709202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00618 (942/152354) while in subpopulation AFR AF= 0.0214 (890/41586). AF 95% confidence interval is 0.0202. There are 14 homozygotes in gnomad4. There are 448 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4 linkuse as main transcript	c.541C>G	p.Gln181Glu	missense_variant	3/6	ENST00000333172.11	NP_619642.2
LOC107984912	XR_002958250.1 linkuse as main transcript	n.87+4674G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11 linkuse as main transcript	c.541C>G	p.Gln181Glu	missense_variant	3/6	1	NM_138697.4	ENSP00000331867	P1	Q7RTX1-1
TAS1R1	ENST00000415267.1 linkuse as main transcript	c.276-1742C>G		intron_variant		1		ENSP00000408448
TAS1R1	ENST00000411823.5 linkuse as main transcript	c.319C>G	p.Gln107Glu	missense_variant	2/3	2		ENSP00000414166
TAS1R1	ENST00000351136.7 linkuse as main transcript	c.499-1742C>G		intron_variant		2		ENSP00000312558		Q7RTX1-2

Frequencies

GnomAD3 genomes

AF:

0.00617

AC:

939

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

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:

0.0000735

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00146

AC:

365

AN:

250658

Hom.:

AF XY:

0.00108

AC XY:

146

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.0203

Gnomad AMR exome

AF:

0.000898

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:

0.0000177

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000591

AC:

863

AN:

1460910

Hom.:

Cov.:

AF XY:

0.000506

AC XY:

368

AN XY:

726616

show subpopulations

Gnomad4 AFR exome

AF:

0.0216

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00618

AC:

942

AN:

152354

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

448

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.000345

Hom.:

Bravo

AF:

0.00697

ESP6500AA

AF:

0.0213

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00185

AC:

225

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 09, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

2.0

DANN

Benign

0.86

DEOGEN2

Benign

0.058

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.67

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.95

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.76

REVEL

Benign

0.15

Sift

Benign

0.27

Sift4G

Benign

0.28

Polyphen

0.062

Vest4

0.067

MVP

0.60

MPC

0.22

ClinPred

0.0047

GERP RS

-2.5

Varity_R

0.13

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over