rs619381

Positions:

• chr12-10801659-C-T

Variant summary

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

The NM_023919.2(TAS2R7):​c.912G>A​(p.Met304Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,609,374 control chromosomes in the GnomAD database, including 12,350 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 0.090 (857 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11493 hom.)
• Consequence: TAS2R7 NM_023919.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

Genes affected

TAS2R7 (HGNC:14913): (taste 2 receptor member 7) This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017491877).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R7	NM_023919.2	c.912G>A	p.Met304Ile	missense_variant	1/1	ENST00000240687.2	NP_076408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R7	ENST00000240687.2	c.912G>A	p.Met304Ile	missense_variant	1/1	6	NM_023919.2	ENSP00000240687.2

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13698 AN: 152090 Hom.: 856 Cov.: 32

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.0672

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0879

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0957

GnomAD3 exomes AF: 0.115 AC: 28743 AN: 250120 Hom.: 1859 AF XY: 0.118 AC XY: 15926 AN XY: 135142

Gnomad AFR exome AF: 0.0235

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.0889

Gnomad SAS exome AF: 0.175

Gnomad FIN exome AF: 0.0531

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.122 AC: 177277 AN: 1457166 Hom.: 11493 Cov.: 31 AF XY: 0.124 AC XY: 89553 AN XY: 725068

Gnomad4 AFR exome AF: 0.0200

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.0558

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.0901 AC: 13708 AN: 152208 Hom.: 857 Cov.: 32 AF XY: 0.0901 AC XY: 6708 AN XY: 74414

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0881

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.115 Hom.: 1991

Bravo AF: 0.0918

TwinsUK AF: 0.121 AC: 447

ALSPAC AF: 0.124 AC: 477

ESP6500AA AF: 0.0277 AC: 122

ESP6500EA AF: 0.121 AC: 1043

ExAC AF: 0.114 AC: 13866

Asia WGS AF: 0.108 AC: 377 AN: 3478

EpiCase AF: 0.116

EpiControl AF: 0.117

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.2
DANN	Benign	0.68
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.018	N
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.011
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.014	D
Polyphen		0.26	B
Vest4		0.057
MutPred		0.21		Loss of catalytic residue at M304 (P = 0.0266);
MPC		0.0039
ClinPred		0.018	T
GERP RS		-0.70
Varity_R		0.16
gMVP		0.070

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: rs619381; hg19: chr12-10954258; COSMIC: COSV53688236; COSMIC: COSV53688236;