rs619381

Variant names:

• chr12-10801659-C-T
• rs619381
• NM_023919.2:c.912G>A

Variant summary

Our verdict is Benign. The variant received -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. 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 0.090 (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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TAS2R7	NM_023919.2	c.912G>A	p.Met304Ile	missense_variant	Exon 1 of 1	ENST00000240687.2	NP_076408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R7	ENST00000240687.2	c.912G>A	p.Met304Ile	missense_variant	Exon 1 of 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

GnomAD2 exomes AF: 0.115 AC: 28743 AN: 250120 AF XY: 0.118

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 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

African (AFR) AF: 0.0200 AC: 669 AN: 33414

American (AMR) AF: 0.150 AC: 6708 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2948 AN: 26092

East Asian (EAS) AF: 0.104 AC: 4138 AN: 39682

South Asian (SAS) AF: 0.179 AC: 15356 AN: 86006

European-Finnish (FIN) AF: 0.0558 AC: 2974 AN: 53308

Middle Eastern (MID) AF: 0.102 AC: 584 AN: 5744

European-Non Finnish (NFE) AF: 0.124 AC: 136914 AN: 1108094

Other (OTH) AF: 0.116 AC: 6986 AN: 60216

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

African (AFR) AF: 0.0252 AC: 1046 AN: 41550

American (AMR) AF: 0.119 AC: 1822 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3470

East Asian (EAS) AF: 0.0881 AC: 457 AN: 5188

South Asian (SAS) AF: 0.184 AC: 887 AN: 4822

European-Finnish (FIN) AF: 0.0568 AC: 603 AN: 10608

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8218 AN: 67986

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.111 Hom.: 2556

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
PhyloP100		-1.0
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
Mutation Taster		=98/2	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: rs619381; hg19: chr12-10954258; COSMIC: COSV53688236; COSMIC: COSV53688236;