Genetic Variant TAS1R1:p.Ala110Val (chr1-6571046-C-T) – 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.329C>T(p.Ala110Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,614,170 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.012 ( 14 hom., cov: 33)

Exomes 𝑓: 0.016 ( 256 hom. )

Consequence

TAS1R1
NM_138697.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.33

Publications

18 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.007791668).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0122 (1860/152306) while in subpopulation NFE AF = 0.0193 (1310/68024). AF 95% confidence interval is 0.0184. There are 14 homozygotes in GnomAd4. There are 840 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R1	NM_138697.4 link	c.329C>T	p.Ala110Val	missense_variant	Exon 2 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.329C>T	p.Ala110Val	missense_variant	Exon 2 of 6	1	NM_138697.4	ENSP00000331867.6	Q7RTX1-1
TAS1R1	ENST00000415267.1 link	c.104C>T	p.Ala35Val	missense_variant	Exon 1 of 4	1		ENSP00000408448.1	H0Y6X0
TAS1R1	ENST00000351136.7 link	c.329C>T	p.Ala110Val	missense_variant	Exon 2 of 5	2		ENSP00000312558.5	Q7RTX1-2
TAS1R1	ENST00000411823.5 link	c.104C>T	p.Ala35Val	missense_variant	Exon 1 of 3	2		ENSP00000414166.1	H7C3W7

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1861

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00290

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0192

Gnomad OTH

AF:

0.0187

GnomAD2 exomes

AF:

0.0118

AC:

2960

AN:

251410

AF XY:

0.0122

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00943

Gnomad ASJ exome

AF:

0.00626

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00356

Gnomad NFE exome

AF:

0.0177

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0163

AC:

23856

AN:

1461864

Hom.:

256

Cov.:

AF XY:

0.0163

AC XY:

11879

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

33480

American (AMR)

AF:

0.0102

AC:

456

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00578

AC:

151

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0109

AC:

936

AN:

86254

European-Finnish (FIN)

AF:

0.00438

AC:

234

AN:

53420

Middle Eastern (MID)

AF:

0.00902

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0189

AC:

21053

AN:

1112006

Other (OTH)

AF:

0.0149

AC:

902

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

1353

2706

4060

5413

6766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

772

1544

2316

3088

3860

<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:

0.0122

AC:

1860

AN:

152306

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

840

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00289

AC:

120

AN:

41562

American (AMR)

AF:

0.0172

AC:

263

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00330

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0193

AC:

1310

AN:

68024

Other (OTH)

AF:

0.0185

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

102

203

305

406

508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0158

Hom.:

Bravo

AF:

0.0122

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0164

AC:

141

ExAC

AF:

0.0118

AC:

1435

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0182

EpiControl

AF:

0.0198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

L;L

PhyloP100

2.3

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.29

Sift

Benign

0.14

T;T

Sift4G

Benign

0.34

T;T

Polyphen

1.0

D;D

Vest4

0.43

MPC

0.54

ClinPred

0.023

GERP RS

5.1

PromoterAI

-0.0018

Neutral

(source)

Varity_R

0.22

gMVP

0.29

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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