1-18859635-G-C

Position:

• chr1-18859635-G-C

Variant summary

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

The NM_152232.6(TAS1R2):​c.26C>G​(p.Ser9Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,614,024 control chromosomes in the GnomAD database, including 494,997 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 0.79 (47250 hom., cov: 34)
  • Exomes 𝑓: 0.78 (447747 hom.)
• Consequence: TAS1R2 NM_152232.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

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=1.7540721E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS1R2	NM_152232.6	c.26C>G	p.Ser9Cys	missense_variant	1/6	ENST00000375371.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS1R2	ENST00000375371.4	c.26C>G	p.Ser9Cys	missense_variant	1/6	2	NM_152232.6	P1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119762 AN: 152136 Hom.: 47218 Cov.: 34

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.814

GnomAD3 exomes AF: 0.782 AC: 196556 AN: 251376 Hom.: 77122 AF XY: 0.781 AC XY: 106066 AN XY: 135876

Gnomad AFR exome AF: 0.815

Gnomad AMR exome AF: 0.830

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.758

Gnomad SAS exome AF: 0.789

Gnomad FIN exome AF: 0.691

Gnomad NFE exome AF: 0.778

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.782 AC: 1142576 AN: 1461770 Hom.: 447747 Cov.: 69 AF XY: 0.781 AC XY: 568299 AN XY: 727206

Gnomad4 AFR exome AF: 0.820

Gnomad4 AMR exome AF: 0.832

Gnomad4 ASJ exome AF: 0.819

Gnomad4 EAS exome AF: 0.717

Gnomad4 SAS exome AF: 0.792

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.783

Gnomad4 OTH exome AF: 0.783

GnomAD4 genome AF: 0.787 AC: 119842 AN: 152254 Hom.: 47250 Cov.: 34 AF XY: 0.783 AC XY: 58268 AN XY: 74450

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.817

Alfa AF: 0.781 Hom.: 34988

Bravo AF: 0.800

TwinsUK AF: 0.785 AC: 2912

ALSPAC AF: 0.791 AC: 3047

ESP6500AA AF: 0.830 AC: 3658

ESP6500EA AF: 0.773 AC: 6650

ExAC AF: 0.780 AC: 94744

Asia WGS AF: 0.764 AC: 2658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.34
DANN	Benign	0.56
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.7	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.12
ClinPred		0.0063	T
GERP RS		1.1
Varity_R		0.062
gMVP		0.59

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: rs9701796; hg19: chr1-19186129; COSMIC: COSV64744050;