1-18854521-G-C

Position:

• chr1-18854521-G-C

Variant summary

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

The NM_152232.6(TAS1R2):​c.949C>G​(p.Arg317Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,613,662 control chromosomes in the GnomAD database, including 78,878 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.29 (6587 hom., cov: 33)
  • Exomes 𝑓: 0.31 (72291 hom.)
• Consequence: TAS1R2 NM_152232.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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=0.0038039684).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R2	NM_152232.6	c.949C>G	p.Arg317Gly	missense_variant	3/6	ENST00000375371.4	NP_689418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R2	ENST00000375371.4	c.949C>G	p.Arg317Gly	missense_variant	3/6	2	NM_152232.6	ENSP00000364520.3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43967 AN: 152038 Hom.: 6585 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.300

GnomAD3 exomes AF: 0.284 AC: 71181 AN: 250596 Hom.: 10628 AF XY: 0.288 AC XY: 39036 AN XY: 135486

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.105

Gnomad SAS exome AF: 0.283

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.311 AC: 454711 AN: 1461506 Hom.: 72291 Cov.: 65 AF XY: 0.310 AC XY: 225698 AN XY: 727052

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.289 AC: 43995 AN: 152156 Hom.: 6587 Cov.: 33 AF XY: 0.285 AC XY: 21238 AN XY: 74390

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.300

Alfa AF: 0.297 Hom.: 5323

Bravo AF: 0.288

TwinsUK AF: 0.332 AC: 1231

ALSPAC AF: 0.322 AC: 1242

ESP6500AA AF: 0.249 AC: 1096

ESP6500EA AF: 0.325 AC: 2795

ExAC AF: 0.288 AC: 35012

Asia WGS AF: 0.190 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.14
Sift	Benign	0.27	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.088
MPC		0.17
ClinPred		0.0096	T
GERP RS		2.8
Varity_R		0.23
gMVP		0.50

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: rs34447754; hg19: chr1-19181015; COSMIC: COSV64744435;