NM_176883.2:c.380C>T

Variant names:

• chr7-143478252-C-T
• rs10278721
• NM_176883.2:c.380C>T

Variant summary

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

The NM_176883.2(TAS2R41):​c.380C>T​(p.Pro127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,772 control chromosomes in the GnomAD database, including 60,758 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 0.22 (4414 hom., cov: 30)
  • Exomes 𝑓: 0.27 (56344 hom.)
• Consequence: TAS2R41 NM_176883.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 33 publications found

Genes affected

TAS2R41 (HGNC:18883): (taste 2 receptor member 41) 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. Chloramphenicol is an agonist for the encoded protein. [provided by RefSeq, Jul 2017]

EPHA1-AS1 (HGNC:27799): (EPHA1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.004470557).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R41	NM_176883.2	c.380C>T	p.Pro127Leu	missense_variant	Exon 1 of 1	ENST00000408916.1	NP_795364.2
EPHA1-AS1	NR_033897.1	n.207-26522C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R41	ENST00000408916.1	c.380C>T	p.Pro127Leu	missense_variant	Exon 1 of 1	6	NM_176883.2	ENSP00000386201.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33213 AN: 151858 Hom.: 4405 Cov.: 30

Gnomad AFR AF: 0.0593

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.232

GnomAD2 exomes AF: 0.266 AC: 66216 AN: 249162 AF XY: 0.270

Gnomad AFR exome AF: 0.0557

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.272

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.275 AC: 401655 AN: 1461796 Hom.: 56344 Cov.: 44 AF XY: 0.277 AC XY: 201114 AN XY: 727204

African (AFR) AF: 0.0509 AC: 1703 AN: 33480

American (AMR) AF: 0.289 AC: 12931 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 6620 AN: 26136

East Asian (EAS) AF: 0.315 AC: 12496 AN: 39698

South Asian (SAS) AF: 0.316 AC: 27287 AN: 86254

European-Finnish (FIN) AF: 0.269 AC: 14354 AN: 53396

Middle Eastern (MID) AF: 0.200 AC: 1152 AN: 5768

European-Non Finnish (NFE) AF: 0.278 AC: 309116 AN: 1111952

Other (OTH) AF: 0.265 AC: 15996 AN: 60394

GnomAD4 genome AF: 0.219 AC: 33237 AN: 151976 Hom.: 4414 Cov.: 30 AF XY: 0.222 AC XY: 16520 AN XY: 74252

African (AFR) AF: 0.0594 AC: 2462 AN: 41474

American (AMR) AF: 0.282 AC: 4307 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1491 AN: 5140

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4810

European-Finnish (FIN) AF: 0.266 AC: 2804 AN: 10554

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19059 AN: 67954

Other (OTH) AF: 0.231 AC: 487 AN: 2106

Alfa AF: 0.257 Hom.: 15756

Bravo AF: 0.209

TwinsUK AF: 0.261 AC: 967

ALSPAC AF: 0.279 AC: 1076

ESP6500AA AF: 0.0595 AC: 232

ESP6500EA AF: 0.273 AC: 2266

ExAC AF: 0.262 AC: 31650

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.039	N
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.0010
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.087
Sift	Benign	0.066	T
Sift4G	Benign	0.085	T
Polyphen		0.42	B
Vest4		0.11
MPC		0.12
ClinPred		0.025	T
GERP RS		1.5
PromoterAI		0.011	Neutral
Varity_R		0.11
gMVP		0.15
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10278721; hg19: chr7-143175345; COSMIC: COSV68765043;