rs28374389

Positions:

• chr1-18849352-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.1456A>G​(p.Ile486Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,740 control chromosomes in the GnomAD database, including 33,166 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (2987 hom., cov: 33)
  • Exomes 𝑓: 0.20 (30179 hom.)
• Consequence: TAS1R2 NM_152232.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.517

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=0.0043367147).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS1R2	NM_152232.6	c.1456A>G	p.Ile486Val	missense_variant	4/6	ENST00000375371.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS1R2	ENST00000375371.4	c.1456A>G	p.Ile486Val	missense_variant	4/6	2	NM_152232.6	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28381 AN: 152108 Hom.: 2978 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.179 AC: 44721 AN: 249630 Hom.: 4530 AF XY: 0.177 AC XY: 23898 AN XY: 135036

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.00190

Gnomad SAS exome AF: 0.106

Gnomad FIN exome AF: 0.252

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.198 AC: 289409 AN: 1461514 Hom.: 30179 Cov.: 34 AF XY: 0.195 AC XY: 141683 AN XY: 727048

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.00156

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.187 AC: 28408 AN: 152226 Hom.: 2987 Cov.: 33 AF XY: 0.187 AC XY: 13920 AN XY: 74422

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0998

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.180

Alfa AF: 0.196 Hom.: 5005

Bravo AF: 0.181

TwinsUK AF: 0.205 AC: 760

ALSPAC AF: 0.217 AC: 837

ESP6500AA AF: 0.148 AC: 654

ESP6500EA AF: 0.206 AC: 1769

ExAC AF: 0.175 AC: 21304

Asia WGS AF: 0.0510 AC: 180 AN: 3478

EpiCase AF: 0.202

EpiControl AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.9
DANN	Benign	0.58
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.15
Sift	Benign	0.28	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.019
MPC		0.10
ClinPred		0.0019	T
GERP RS		-1.9
Varity_R		0.037
gMVP		0.18

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: rs28374389; hg19: chr1-19175846; COSMIC: COSV64744897;