chr1-18859635-G-C

Variant names:

• chr1-18859635-G-C
• rs9701796
• NM_152232.6:c.26C>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.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. 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 0.79 (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
• Publications: 43 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=1.7540721E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.816 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R2	NM_152232.6	MANE Select	c.26C>G	p.Ser9Cys	missense	Exon 1 of 6	NP_689418.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R2	ENST00000375371.4	TSL:2 MANE Select	c.26C>G	p.Ser9Cys	missense	Exon 1 of 6	ENSP00000364520.3

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

GnomAD2 exomes AF: 0.782 AC: 196556 AN: 251376 AF XY: 0.781

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 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

African (AFR) AF: 0.820 AC: 27445 AN: 33474

American (AMR) AF: 0.832 AC: 37219 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 21401 AN: 26136

East Asian (EAS) AF: 0.717 AC: 28483 AN: 39698

South Asian (SAS) AF: 0.792 AC: 68333 AN: 86254

European-Finnish (FIN) AF: 0.688 AC: 36763 AN: 53414

Middle Eastern (MID) AF: 0.815 AC: 4703 AN: 5768

European-Non Finnish (NFE) AF: 0.783 AC: 870924 AN: 1111916

Other (OTH) AF: 0.783 AC: 47305 AN: 60390

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

African (AFR) AF: 0.817 AC: 33940 AN: 41528

American (AMR) AF: 0.828 AC: 12674 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2833 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3906 AN: 5166

South Asian (SAS) AF: 0.799 AC: 3854 AN: 4824

European-Finnish (FIN) AF: 0.686 AC: 7281 AN: 10616

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52588 AN: 68018

Other (OTH) AF: 0.817 AC: 1728 AN: 2116

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 v4.9

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	0.0000017	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.7	N
PhyloP100		-0.020
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
PromoterAI		-0.021	Neutral
Varity_R		0.062
gMVP		0.59
Mutation Taster		=99/1	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: rs9701796; hg19: chr1-19186129; COSMIC: COSV64744050;