Genetic Variant TAS1R1:p.Cys4Tyr (chr1-6555384-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.11G>A(p.Cys4Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,599,866 control chromosomes in the GnomAD database, including 67 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.

Frequency

Genomes: 𝑓 0.013 ( 30 hom., cov: 34)

Exomes 𝑓: 0.0056 ( 37 hom. )

Consequence

TAS1R1
NM_138697.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

4 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:

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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=0.0029952526).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1911/152382) while in subpopulation AFR AF = 0.0341 (1418/41594). AF 95% confidence interval is 0.0326. There are 30 homozygotes in GnomAd4. There are 904 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R1	NM_138697.4 link	c.11G>A	p.Cys4Tyr	missense_variant	Exon 1 of 6	ENST00000333172.11	NP_619642.2	Q7RTX1-1
TAS1R1	NM_177540.3 link	c.11G>A	p.Cys4Tyr	missense_variant	Exon 1 of 5		NP_803884.1	Q7RTX1-2A8K7J9
TAS1R1	XM_011542206.3 link	c.11G>A	p.Cys4Tyr	missense_variant	Exon 1 of 6		XP_011540508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11 link	c.11G>A	p.Cys4Tyr	missense_variant	Exon 1 of 6	1	NM_138697.4	ENSP00000331867.6		Q7RTX1-1
TAS1R1	ENST00000351136.7 link	c.11G>A	p.Cys4Tyr	missense_variant	Exon 1 of 5	2		ENSP00000312558.5		Q7RTX1-2

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1903

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00513

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00544

AC:

1259

AN:

231386

AF XY:

0.00483

show subpopulations

Gnomad AFR exome

AF:

0.0343

Gnomad AMR exome

AF:

0.00277

Gnomad ASJ exome

AF:

0.00458

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00189

Gnomad NFE exome

AF:

0.00470

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00556

AC:

8045

AN:

1447484

Hom.:

Cov.:

AF XY:

0.00532

AC XY:

3826

AN XY:

719210

show subpopulations

African (AFR)

AF:

0.0318

AC:

1058

AN:

33294

American (AMR)

AF:

0.00296

AC:

129

AN:

43652

Ashkenazi Jewish (ASJ)

AF:

0.00471

AC:

122

AN:

25876

East Asian (EAS)

AF:

0.00

AC:

AN:

39198

South Asian (SAS)

AF:

0.00303

AC:

256

AN:

84562

European-Finnish (FIN)

AF:

0.00208

AC:

101

AN:

48598

Middle Eastern (MID)

AF:

0.00534

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00540

AC:

5977

AN:

1106864

Other (OTH)

AF:

0.00622

AC:

372

AN:

59826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

456

913

1369

1826

2282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

248

496

744

992

1240

<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:

0.0125

AC:

1911

AN:

152382

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

904

AN XY:

74526

show subpopulations

African (AFR)

AF:

0.0341

AC:

1418

AN:

41594

American (AMR)

AF:

0.00523

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00269

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00513

AC:

349

AN:

68042

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

101

202

302

403

504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00776

Hom.:

Bravo

AF:

0.0130

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.0325

AC:

143

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00570

AC:

689

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.021

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.046

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.44

PhyloP100

-1.3

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.20

Sift

Benign

0.97

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.20

MVP

0.26

MPC

0.28

ClinPred

0.0070

GERP RS

-4.9

PromoterAI

-0.069

Neutral

(source)

Varity_R

0.10

gMVP

0.65

Mutation Taster

=100/0

polymorphism

(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