rs35118458

Variant names:

• chr1-6576996-G-A
• rs35118458
• NM_138697.4:c.1520G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-6576996-G-A
• chr1-6576996-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.018 (47 hom., cov: 34)
  • Exomes 𝑓: 0.025 (523 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 17 publications found

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]

LOC107984912 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 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. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138697.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	NM_138697.4	MANE Select	c.1520G>A	p.Arg507Gln	missense	Exon 5 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.758G>A	p.Arg253Gln	missense	Exon 4 of 5	NP_803884.1	Q7RTX1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	ENST00000333172.11	TSL:1 MANE Select	c.1520G>A	p.Arg507Gln	missense	Exon 5 of 6	ENSP00000331867.6	Q7RTX1-1
	TAS1R1	ENST00000415267.1	TSL:1	c.533G>A	p.Arg178Gln	missense	Exon 3 of 4	ENSP00000408448.1	H0Y6X0
	TAS1R1	ENST00000351136.7	TSL:2	c.758G>A	p.Arg253Gln	missense	Exon 4 of 5	ENSP00000312558.5	Q7RTX1-2

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2688 AN: 152232 Hom.: 47 Cov.: 34

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

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.: 32 AF XY: 0.0242 AC XY: 17595 AN XY: 727246

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: 2 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

GnomAD4 genome AF: 0.0176 AC: 2686 AN: 152350 Hom.: 47 Cov.: 34 AF XY: 0.0169 AC XY: 1257 AN XY: 74496

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: 1 AN: 5192

South Asian (SAS) AF: 0.0221 AC: 107 AN: 4832

European-Finnish (FIN) AF: 0.00791 AC: 84 AN: 10620

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0257 AC: 1750 AN: 68030

Other (OTH) AF: 0.0170 AC: 36 AN: 2112

Alfa AF: 0.0237 Hom.: 95

Bravo AF: 0.0185

TwinsUK AF: 0.0235 AC: 87

ALSPAC AF: 0.0244 AC: 94

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.0269 AC: 231

ExAC AF: 0.0201 AC: 2445

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0261

EpiControl AF: 0.0261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.9
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.19
Sift	Benign	0.050	D
Sift4G	Benign	0.083	T
Polyphen		0.94	P
Vest4		0.12
MPC		0.47
ClinPred		0.011	T
GERP RS		2.9
Varity_R		0.18
gMVP		0.50
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35118458; hg19: chr1-6637056; COSMIC: COSV99048210; COSMIC: COSV99048210;