1-18854521-G-C

Variant names:

• chr1-18854521-G-C
• rs34447754
• NM_152232.6:c.949C>G

Variant summary

Our verdict is Benign. The variant received -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. 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 0.29 (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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152232.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R2	NM_152232.6	MANE Select	c.949C>G	p.Arg317Gly	missense	Exon 3 of 6	NP_689418.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R2	ENST00000375371.4	TSL:2 MANE Select	c.949C>G	p.Arg317Gly	missense	Exon 3 of 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

GnomAD2 exomes AF: 0.284 AC: 71181 AN: 250596 AF XY: 0.288

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 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

African (AFR) AF: 0.259 AC: 8682 AN: 33478

American (AMR) AF: 0.243 AC: 10850 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 8659 AN: 26126

East Asian (EAS) AF: 0.118 AC: 4692 AN: 39696

South Asian (SAS) AF: 0.277 AC: 23887 AN: 86242

European-Finnish (FIN) AF: 0.290 AC: 15443 AN: 53198

Middle Eastern (MID) AF: 0.307 AC: 1772 AN: 5768

European-Non Finnish (NFE) AF: 0.326 AC: 362581 AN: 1111912

Other (OTH) AF: 0.300 AC: 18145 AN: 60388

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

African (AFR) AF: 0.261 AC: 10835 AN: 41508

American (AMR) AF: 0.267 AC: 4092 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1185 AN: 3472

East Asian (EAS) AF: 0.106 AC: 550 AN: 5180

South Asian (SAS) AF: 0.251 AC: 1210 AN: 4826

European-Finnish (FIN) AF: 0.281 AC: 2979 AN: 10596

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22028 AN: 67960

Other (OTH) AF: 0.300 AC: 633 AN: 2110

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 v4.9

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
PhyloP100		0.039
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
Mutation Taster		=95/5	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: rs34447754; hg19: chr1-19181015; COSMIC: COSV64744435;