rs35375392

Positions:

• chr1-6555384-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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. 14/19 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.11G>A	p.Cys4Tyr	missense_variant	1/6	ENST00000333172.11	NP_619642.2
TAS1R1	NM_177540.3	c.11G>A	p.Cys4Tyr	missense_variant	1/5		NP_803884.1
TAS1R1	XM_011542206.3	c.11G>A	p.Cys4Tyr	missense_variant	1/6		XP_011540508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.11G>A	p.Cys4Tyr	missense_variant	1/6	1	NM_138697.4	ENSP00000331867	P1
TAS1R1	ENST00000351136.7	c.11G>A	p.Cys4Tyr	missense_variant	1/5	2		ENSP00000312558

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1903 AN: 152264 Hom.: 29 Cov.: 34

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

GnomAD3 exomes AF: 0.00544 AC: 1259 AN: 231386 Hom.: 13 AF XY: 0.00483 AC XY: 608 AN XY: 125976

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 SAS exome AF: 0.00272

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.: 37 Cov.: 30 AF XY: 0.00532 AC XY: 3826 AN XY: 719210

Gnomad4 AFR exome AF: 0.0318

Gnomad4 AMR exome AF: 0.00296

Gnomad4 ASJ exome AF: 0.00471

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00303

Gnomad4 FIN exome AF: 0.00208

Gnomad4 NFE exome AF: 0.00540

Gnomad4 OTH exome AF: 0.00622

GnomAD4 genome AF: 0.0125 AC: 1911 AN: 152382 Hom.: 30 Cov.: 34 AF XY: 0.0121 AC XY: 904 AN XY: 74526

Gnomad4 AFR AF: 0.0341

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00513

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00600 Hom.: 10

Bravo AF: 0.0130

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.0325 AC: 143

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00570 AC: 689

Asia WGS AF: 0.00346 AC: 12 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	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.021
DANN	Benign	0.63
DEOGEN2	Benign	0.046	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.61	T;T
MetaRNN	Benign	0.0030	T;T
MetaSVM	Benign	-0.44	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
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	T
GERP RS		-4.9
Varity_R		0.10
gMVP		0.65

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

Other links and lift over

dbSNP: rs35375392; hg19: chr1-6615444;