dbSNP rs34160967: TAS1R1:p.Ala372Thr (chr1-6575246-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138697.4(TAS1R1):c.1114G>A(p.Ala372Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,466 control chromosomes in the GnomAD database, including 16,835 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1389 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15446 hom. )

Consequence

TAS1R1
NM_138697.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002396077).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R1	NM_138697.4 link	c.1114G>A	p.Ala372Thr	missense_variant	Exon 3 of 6	ENST00000333172.11	NP_619642.2	Q7RTX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAS1R1	ENST00000333172.11 link	c.1114G>A	p.Ala372Thr	missense_variant	Exon 3 of 6	1	NM_138697.4	ENSP00000331867.6	Q7RTX1-1
TAS1R1	ENST00000415267.1 link	c.274-1169G>A		intron_variant	Intron 1 of 3	1		ENSP00000408448.1	H0Y6X0
TAS1R1	ENST00000411823.5 link	c.889G>A	p.Ala297Thr	missense_variant	Exon 2 of 3	2		ENSP00000414166.1	H7C3W7
TAS1R1	ENST00000351136.7 link	c.499-1169G>A		intron_variant	Intron 2 of 4	2		ENSP00000312558.5	Q7RTX1-2

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18302

AN:

152184

Hom.:

1390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0743

Gnomad ASJ

AF:

0.0835

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.0990

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.0970

GnomAD3 exomes

AF:

0.131

AC:

32862

AN:

250040

Hom.:

2841

AF XY:

0.131

AC XY:

17739

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.0698

Gnomad AMR exome

AF:

0.0502

Gnomad ASJ exome

AF:

0.0805

Gnomad EAS exome

AF:

0.313

Gnomad SAS exome

AF:

0.0990

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.136

AC:

198466

AN:

1461164

Hom.:

15446

Cov.:

AF XY:

0.135

AC XY:

97998

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.0697

Gnomad4 AMR exome

AF:

0.0516

Gnomad4 ASJ exome

AF:

0.0839

Gnomad4 EAS exome

AF:

0.346

Gnomad4 SAS exome

AF:

0.0983

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.120

AC:

18301

AN:

152302

Hom.:

1389

Cov.:

AF XY:

0.122

AC XY:

9093

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0703

Gnomad4 AMR

AF:

0.0741

Gnomad4 ASJ

AF:

0.0835

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.0989

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.0979

Alfa

AF:

0.132

Hom.:

1826

Bravo

AF:

0.109

TwinsUK

AF:

0.122

AC:

453

ALSPAC

AF:

0.141

AC:

543

ESP6500AA

AF:

0.0690

AC:

304

ESP6500EA

AF:

0.126

AC:

1080

ExAC

AF:

0.133

AC:

16172

Asia WGS

AF:

0.182

AC:

634

AN:

3478

EpiCase

AF:

0.122

EpiControl

AF:

0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.54

DANN

Benign

0.76

DEOGEN2

Benign

0.054

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.40

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.65

REVEL

Benign

0.26

Sift

Benign

0.43

Sift4G

Benign

0.67

Polyphen

0.16

Vest4

0.073

MPC

0.17

ClinPred

0.0020

GERP RS

-0.64

Varity_R

0.050

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over