rs35874116

chr1-18854899-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152232.6(TAS1R2):c.571A>G(p.Ile191Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,612,726 control chromosomes in the GnomAD database, including 83,033 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.31 (7487 hom., cov: 33)
  • Exomes 𝑓: 0.32 (75546 hom.)
• Consequence: TAS1R2 NM_152232.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486

Genes affected

TAS1R2 (HGNC:14905): (taste 1 receptor member 2) Contributes to sweet taste receptor activity. Involved in detection of chemical stimulus involved in sensory perception of sweet taste and positive regulation of cytokinesis. Part of sweet taste receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.0253353E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS1R2	NM_152232.6	c.571A>G	p.Ile191Val	missense_variant	3/6	ENST00000375371.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS1R2	ENST00000375371.4	c.571A>G	p.Ile191Val	missense_variant	3/6	2	NM_152232.6	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47010 AN: 152022 Hom.: 7484 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.314

GnomAD3 exomes AF: 0.294 AC: 73268 AN: 249498 Hom.: 11312 AF XY: 0.298 AC XY: 40166 AN XY: 134994

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.303

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.318 AC: 464945 AN: 1460586 Hom.: 75546 Cov.: 58 AF XY: 0.318 AC XY: 230784 AN XY: 726462

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.309 AC: 47046 AN: 152140 Hom.: 7487 Cov.: 33 AF XY: 0.305 AC XY: 22663 AN XY: 74382

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.314

Alfa AF: 0.321 Hom.: 12358

Bravo AF: 0.310

TwinsUK AF: 0.334 AC: 1239

ALSPAC AF: 0.326 AC: 1255

ESP6500AA AF: 0.306 AC: 1349

ESP6500EA AF: 0.331 AC: 2845

ExAC AF: 0.299 AC: 36323

Asia WGS AF: 0.211 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	0.024
Dann	Benign	0.34
DEOGEN2	Benign	0.044	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.00090	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.033
MPC		0.10
ClinPred		0.0022	T
GERP RS		-4.1
Varity_R		0.022
gMVP		0.36

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: rs35874116; hg19: chr1-19181393; COSMIC: COSV64744677;