1-18840399-C-T

Position:

• chr1-18840399-C-T

Variant summary

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

The NM_152232.6(TAS1R2):​c.1720G>A​(p.Ala574Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 1,614,106 control chromosomes in the GnomAD database, including 3,111 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.057 (306 hom., cov: 33)
  • Exomes 𝑓: 0.053 (2805 hom.)
• Consequence: TAS1R2 NM_152232.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

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=0.0049642324).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R2	NM_152232.6	c.1720G>A	p.Ala574Thr	missense_variant	6/6	ENST00000375371.4	NP_689418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R2	ENST00000375371.4	c.1720G>A	p.Ala574Thr	missense_variant	6/6	2	NM_152232.6	ENSP00000364520	P1

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8664 AN: 152154 Hom.: 302 Cov.: 33

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.0335

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0478

GnomAD3 exomes AF: 0.0651 AC: 16352 AN: 251126 Hom.: 819 AF XY: 0.0701 AC XY: 9512 AN XY: 135788

Gnomad AFR exome AF: 0.0610

Gnomad AMR exome AF: 0.0199

Gnomad ASJ exome AF: 0.0350

Gnomad EAS exome AF: 0.0990

Gnomad SAS exome AF: 0.162

Gnomad FIN exome AF: 0.0840

Gnomad NFE exome AF: 0.0474

Gnomad OTH exome AF: 0.0556

GnomAD4 exome AF: 0.0526 AC: 76908 AN: 1461834 Hom.: 2805 Cov.: 37 AF XY: 0.0560 AC XY: 40699 AN XY: 727220

Gnomad4 AFR exome AF: 0.0641

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0367

Gnomad4 EAS exome AF: 0.0801

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.0867

Gnomad4 NFE exome AF: 0.0432

Gnomad4 OTH exome AF: 0.0567

GnomAD4 genome AF: 0.0571 AC: 8699 AN: 152272 Hom.: 306 Cov.: 33 AF XY: 0.0589 AC XY: 4388 AN XY: 74438

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.0309

Gnomad4 ASJ AF: 0.0335

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0760

Gnomad4 NFE AF: 0.0471

Gnomad4 OTH AF: 0.0491

Alfa AF: 0.0470 Hom.: 395

Bravo AF: 0.0503

TwinsUK AF: 0.0453 AC: 168

ALSPAC AF: 0.0493 AC: 190

ESP6500AA AF: 0.0663 AC: 292

ESP6500EA AF: 0.0463 AC: 398

ExAC AF: 0.0683 AC: 8292

Asia WGS AF: 0.138 AC: 478 AN: 3478

EpiCase AF: 0.0471

EpiControl AF: 0.0468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.15
DANN	Benign	0.79
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.14
Sift	Benign	0.91	T
Sift4G	Benign	0.57	T
Polyphen		0.11	B
Vest4		0.025
MPC		0.12
ClinPred		0.0018	T
GERP RS		-2.4
Varity_R		0.045
gMVP		0.26

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: rs6662276; hg19: chr1-19166893; COSMIC: COSV64744404;