NM_152232.6:c.1456A>G

Variant names:

• chr1-18849352-T-C
• rs28374389
• NM_152232.6:c.1456A>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.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. 16/21 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 0.19 (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
• Publications: 17 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=0.0043367147).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R2	NM_152232.6	MANE Select	c.1456A>G	p.Ile486Val	missense	Exon 4 of 6	NP_689418.2	Q8TE23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R2	ENST00000375371.4	TSL:2 MANE Select	c.1456A>G	p.Ile486Val	missense	Exon 4 of 6	ENSP00000364520.3	Q8TE23

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

GnomAD2 exomes AF: 0.179 AC: 44721 AN: 249630 AF XY: 0.177

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 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

African (AFR) AF: 0.144 AC: 4826 AN: 33478

American (AMR) AF: 0.209 AC: 9365 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5151 AN: 26132

East Asian (EAS) AF: 0.00156 AC: 62 AN: 39700

South Asian (SAS) AF: 0.109 AC: 9382 AN: 86244

European-Finnish (FIN) AF: 0.250 AC: 13285 AN: 53246

Middle Eastern (MID) AF: 0.110 AC: 626 AN: 5674

European-Non Finnish (NFE) AF: 0.212 AC: 235319 AN: 1111952

Other (OTH) AF: 0.189 AC: 11393 AN: 60378

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

African (AFR) AF: 0.145 AC: 6044 AN: 41546

American (AMR) AF: 0.216 AC: 3303 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5182

South Asian (SAS) AF: 0.0998 AC: 481 AN: 4822

European-Finnish (FIN) AF: 0.266 AC: 2822 AN: 10602

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14423 AN: 67990

Other (OTH) AF: 0.180 AC: 380 AN: 2112

Alfa AF: 0.194 Hom.: 6690

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 v4.9

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
PhyloP100		-0.52
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
Mutation Taster		=100/0	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: rs28374389; hg19: chr1-19175846; COSMIC: COSV64744897;