5-9629611-C-T

Position:

chr5-9629611-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_019599.3(TAS2R1):c.422G>A(p.Cys141Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,078 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0064 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 13 hom. )

Consequence

TAS2R1
NM_019599.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.353

Variant links:

Genes affected

TAS2R1 (HGNC:14909): (taste 2 receptor member 1) This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily and that are specifically expressed by taste receptor cells of the tongue and palate epithelia. This intronless taste receptor gene encodes a 7-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is mapped to chromosome 5p15, the location of a genetic locus (PROP) that controls the detection of the bitter compound 6-n-propyl-2-thiouracil. [provided by RefSeq, Jul 2008]

TAS2R1 links:

ENSG00000248525 (HGNC:):

ENSG00000248525 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040967166).

BP6

Variant 5-9629611-C-T is Benign according to our data. Variant chr5-9629611-C-T is described in ClinVar as [Benign]. Clinvar id is 785113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00645 (981/152200) while in subpopulation AFR AF= 0.0222 (923/41516). AF 95% confidence interval is 0.021. There are 10 homozygotes in gnomad4. There are 453 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R1	NM_019599.3 link	c.422G>A	p.Cys141Tyr	missense_variant	1/1	ENST00000382492.4	NP_062545.1	Q9NYW7Q502V6
TAS2R1	NM_001386348.1 link	c.302G>A	p.Cys101Tyr	missense_variant	10/10		NP_001373277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAS2R1	ENST00000382492.4 link	c.422G>A	p.Cys141Tyr	missense_variant	1/1	6	NM_019599.3	ENSP00000371932.2	Q9NYW7
TAS2R1	ENST00000514078.1 link	c.302G>A	p.Cys101Tyr	missense_variant	2/2	3		ENSP00000476190.1	U3KQT0
ENSG00000248525	ENST00000504182.2 link	n.36-6009G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00645

AC:

981

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00176

AC:

441

AN:

250972

Hom.:

AF XY:

0.00123

AC XY:

167

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000690

AC:

1009

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000572

AC XY:

416

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0240

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00645

AC:

981

AN:

152200

Hom.:

Cov.:

AF XY:

0.00609

AC XY:

453

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0222

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00734

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00222

AC:

270

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.3

DANN

Benign

0.68

DEOGEN2

Benign

0.0018

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.033

Sift

Uncertain

0.016

D;.

Sift4G

Benign

1.0

T;.

Polyphen

0.41

B;.

Vest4

0.18

MVP

0.13

MPC

0.10

ClinPred

0.0074

GERP RS

0.44

Varity_R

0.27

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over