NM_138697.4:c.1520G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 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. 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
• 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 -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	c.1520G>A	p.Arg507Gln	missense_variant	Exon 5 of 6	ENST00000333172.11	NP_619642.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.1520G>A	p.Arg507Gln	missense_variant	Exon 5 of 6	1	NM_138697.4	ENSP00000331867.6
TAS1R1	ENST00000415267.1	c.533G>A	p.Arg178Gln	missense_variant	Exon 3 of 4	1		ENSP00000408448.1
TAS1R1	ENST00000351136.7	c.758G>A	p.Arg253Gln	missense_variant	Exon 4 of 5	2		ENSP00000312558.5
TAS1R1	ENST00000411823.5	c.1035+1604G>A		intron_variant	Intron 2 of 2	2		ENSP00000414166.1

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 v4.3

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;T
MetaRNN	Benign	0.0023	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.4	L;.
PhyloP100		1.9
PrimateAI	Benign	0.29	T
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	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;