rs10260248

Positions:

• chr7-143222638-C-A

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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 0.084 (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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R40	NM_176882.2	c.560C>A	p.Ser187Tyr	missense_variant	1/1	ENST00000408947.4	NP_795363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R40	ENST00000408947.4	c.560C>A	p.Ser187Tyr	missense_variant	1/1		NM_176882.2	ENSP00000386210	P1

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

GnomAD3 exomes AF: 0.0680 AC: 16945 AN: 249214 Hom.: 720 AF XY: 0.0679 AC XY: 9174 AN XY: 135194

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 SAS exome AF: 0.0958

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

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0740

Gnomad4 ASJ exome AF: 0.0544

Gnomad4 EAS exome AF: 0.0192

Gnomad4 SAS exome AF: 0.0963

Gnomad4 FIN exome AF: 0.0298

Gnomad4 NFE exome AF: 0.0611

Gnomad4 OTH exome AF: 0.0633

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

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0696

Gnomad4 ASJ AF: 0.0556

Gnomad4 EAS AF: 0.0252

Gnomad4 SAS AF: 0.0967

Gnomad4 FIN AF: 0.0305

Gnomad4 NFE AF: 0.0628

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0663 Hom.: 775

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 v4.3

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
MutationTaster	Benign	1.0	P
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

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: rs10260248; hg19: chr7-142919731; COSMIC: COSV68818390; COSMIC: COSV68818390;