rs10260248

Variant names:

• chr7-143222638-C-A
• rs10260248
• NM_176882.2:c.560C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176882.2(TAS2R40):​c.560C>A​(p.Ser187Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 1,614,064 control chromosomes in the GnomAD database, including 3,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.084 (637 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3292 hom.)
• Consequence: TAS2R40 NM_176882.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 19 publications found

Genes affected

TAS2R40 (HGNC:18885): (taste 2 receptor member 40) This gene encodes a member of the bitter taste receptor family which belong to the G protein-coupled receptor superfamily and are predominantly expressed in taste receptor cells of the tongue and palate epithelia. This intronless taste receptor gene encodes a seven-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered together with eight other taste receptor genes on chromosome 7. A decrease in the expression of this gene is associated with hypogeusia. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015716851).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176882.2. 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
	TAS2R40	NM_176882.2	MANE Select	c.560C>A	p.Ser187Tyr	missense	Exon 1 of 1	NP_795363.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R40	ENST00000408947.4	TSL:6 MANE Select	c.560C>A	p.Ser187Tyr	missense	Exon 1 of 1	ENSP00000386210.3

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12783 AN: 152084 Hom.: 637 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.0251

Gnomad SAS AF: 0.0958

Gnomad FIN AF: 0.0305

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0703

GnomAD2 exomes AF: 0.0680 AC: 16945 AN: 249214 AF XY: 0.0679

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0739

Gnomad ASJ exome AF: 0.0541

Gnomad EAS exome AF: 0.0262

Gnomad FIN exome AF: 0.0294

Gnomad NFE exome AF: 0.0640

Gnomad OTH exome AF: 0.0592

GnomAD4 exome AF: 0.0632 AC: 92390 AN: 1461862 Hom.: 3292 Cov.: 31 AF XY: 0.0639 AC XY: 46483 AN XY: 727238

African (AFR) AF: 0.143 AC: 4782 AN: 33478

American (AMR) AF: 0.0740 AC: 3311 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0544 AC: 1423 AN: 26136

East Asian (EAS) AF: 0.0192 AC: 764 AN: 39700

South Asian (SAS) AF: 0.0963 AC: 8307 AN: 86258

European-Finnish (FIN) AF: 0.0298 AC: 1590 AN: 53412

Middle Eastern (MID) AF: 0.0777 AC: 448 AN: 5768

European-Non Finnish (NFE) AF: 0.0611 AC: 67944 AN: 1111992

Other (OTH) AF: 0.0633 AC: 3821 AN: 60396

GnomAD4 genome AF: 0.0841 AC: 12793 AN: 152202 Hom.: 637 Cov.: 32 AF XY: 0.0815 AC XY: 6066 AN XY: 74402

African (AFR) AF: 0.147 AC: 6118 AN: 41528

American (AMR) AF: 0.0696 AC: 1064 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3470

East Asian (EAS) AF: 0.0252 AC: 130 AN: 5166

South Asian (SAS) AF: 0.0967 AC: 466 AN: 4818

European-Finnish (FIN) AF: 0.0305 AC: 323 AN: 10606

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0628 AC: 4273 AN: 68004

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

Alfa AF: 0.0683 Hom.: 1673

Bravo AF: 0.0893

TwinsUK AF: 0.0561 AC: 208

ALSPAC AF: 0.0659 AC: 254

ESP6500AA AF: 0.134 AC: 509

ESP6500EA AF: 0.0594 AC: 491

ExAC AF: 0.0711 AC: 8593

Asia WGS AF: 0.0560 AC: 197 AN: 3478

EpiCase AF: 0.0634

EpiControl AF: 0.0684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.20
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.85
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.081
Sift	Benign	0.93	T
Sift4G	Uncertain	0.050	T
Polyphen		0.76	P
Vest4		0.058
MPC		0.16
ClinPred		0.062	T
GERP RS		2.1
Varity_R		0.11
gMVP		0.17
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: rs10260248; hg19: chr7-142919731; COSMIC: COSV68818390; COSMIC: COSV68818390;