dbSNP rs35118458: TAS1R1:p.Arg507Gln (chr1-6576996-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_138697.4(TAS1R1):c.1520G>A(p.Arg507Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,614,234 control chromosomes in the GnomAD database, including 570 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.018 ( 47 hom., cov: 34)

Exomes 𝑓: 0.025 ( 523 hom. )

Consequence

TAS1R1
NM_138697.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.91

Publications

17 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023093224).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0176 (2686/152350) while in subpopulation NFE AF = 0.0257 (1750/68030). AF 95% confidence interval is 0.0247. There are 47 homozygotes in GnomAd4. There are 1257 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R1	NM_138697.4 link	c.1520G>A	p.Arg507Gln	missense_variant	Exon 5 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.1520G>A	p.Arg507Gln	missense_variant	Exon 5 of 6	1	NM_138697.4	ENSP00000331867.6	Q7RTX1-1
TAS1R1	ENST00000415267.1 link	c.533G>A	p.Arg178Gln	missense_variant	Exon 3 of 4	1		ENSP00000408448.1	H0Y6X0
TAS1R1	ENST00000351136.7 link	c.758G>A	p.Arg253Gln	missense_variant	Exon 4 of 5	2		ENSP00000312558.5	Q7RTX1-2
TAS1R1	ENST00000411823.5 link	c.1035+1604G>A		intron_variant	Intron 2 of 2	2		ENSP00000414166.1	H7C3W7

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2688

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00468

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0221

Gnomad FIN

AF:

0.00791

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.0188

AC:

4717

AN:

251478

AF XY:

0.0193

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.0310

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00915

Gnomad NFE exome

AF:

0.0273

Gnomad OTH exome

AF:

0.0223

GnomAD4 exome

AF:

0.0246

AC:

35944

AN:

1461884

Hom.:

523

Cov.:

AF XY:

0.0242

AC XY:

17595

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00376

AC:

126

AN:

33480

American (AMR)

AF:

0.0127

AC:

567

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0318

AC:

832

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0180

AC:

1553

AN:

86258

European-Finnish (FIN)

AF:

0.0103

AC:

548

AN:

53420

Middle Eastern (MID)

AF:

0.0220

AC:

127

AN:

5768

European-Non Finnish (NFE)

AF:

0.0276

AC:

30715

AN:

1112006

Other (OTH)

AF:

0.0244

AC:

1474

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2073

4146

6218

8291

10364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1132

2264

3396

4528

5660

<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:

0.0176

AC:

2686

AN:

152350

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1257

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00467

AC:

194

AN:

41580

American (AMR)

AF:

0.0186

AC:

285

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

116

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.0221

AC:

107

AN:

4832

European-Finnish (FIN)

AF:

0.00791

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0257

AC:

1750

AN:

68030

Other (OTH)

AF:

0.0170

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

143

287

430

574

717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0237

Hom.:

Bravo

AF:

0.0185

TwinsUK

AF:

0.0235

AC:

ALSPAC

AF:

0.0244

AC:

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0269

AC:

231

ExAC

AF:

0.0201

AC:

2445

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0261

EpiControl

AF:

0.0261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.4

L;.

PhyloP100

1.9

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.19

Sift

Benign

0.050

D;T

Sift4G

Benign

0.083

T;T

Polyphen

0.94

P;B

Vest4

0.12

MPC

0.47

ClinPred

0.011

GERP RS

2.9

Varity_R

0.18

gMVP

0.50

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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