chr7-143478252-C-T

Position:

• chr7-143478252-C-T

Variant summary

Our verdict is Benign. Variant got -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. 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 0.22 (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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TAS2R41	NM_176883.2	c.380C>T	p.Pro127Leu	missense_variant	1/1	ENST00000408916.1	NP_795364.2
EPHA1-AS1	NR_033897.1	n.207-26522C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R41	ENST00000408916.1	c.380C>T	p.Pro127Leu	missense_variant	1/1	6	NM_176883.2	ENSP00000386201.1
EPHA1-AS1	ENST00000429289.5	n.207-26522C>T		intron_variant		1
EPHA1-AS1	ENST00000690912.1	n.228-17714C>T		intron_variant
EPHA1-AS1	ENST00000703017.1	n.206-17714C>T		intron_variant

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

GnomAD3 exomes AF: 0.266 AC: 66216 AN: 249162 Hom.: 9225 AF XY: 0.270 AC XY: 36545 AN XY: 135172

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 SAS exome AF: 0.319

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

Gnomad4 AFR exome AF: 0.0509

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.315

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.265

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

Gnomad4 AFR AF: 0.0594

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.231

Alfa AF: 0.268 Hom.: 11670

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
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
Varity_R		0.11
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs10278721; hg19: chr7-143175345; COSMIC: COSV68765043;