rs41278022

Positions:

• chr1-6578865-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_138697.4(TAS1R1):​c.1807C>T​(p.Arg603Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,608,798 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0074 (59 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.156

Genes affected

TAS1R1 (HGNC:14448): (taste 1 receptor member 1) The protein encoded by this gene is a G protein-coupled receptor and is a component of the heterodimeric amino acid taste receptor T1R1+3. The T1R1+3 receptor responds to L-amino acids but not to D-enantiomers or other compounds. Most amino acids that are perceived as sweet activate T1R1+3, and this activation is strictly dependent on an intact T1R1+3 heterodimer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

LOC107984912 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013943106).
• BP6: Variant 1-6578865-C-T is Benign according to our data. Variant chr1-6578865-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 767648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.1807C>T	p.Arg603Cys	missense_variant	6/6	ENST00000333172.11	NP_619642.2
LOC107984912	XR_002958250.1	n.87+482G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.1807C>T	p.Arg603Cys	missense_variant	6/6	1	NM_138697.4	ENSP00000331867	P1
TAS1R1	ENST00000415267.1	c.610-431C>T		intron_variant		1		ENSP00000408448
TAS1R1	ENST00000351136.7	c.1045C>T	p.Arg349Cys	missense_variant	5/5	2		ENSP00000312558
TAS1R1	ENST00000411823.5	c.*30C>T		3_prime_UTR_variant	3/3	2		ENSP00000414166

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 841 AN: 152090 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00754

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00935

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00611 AC: 1517 AN: 248086 Hom.: 11 AF XY: 0.00629 AC XY: 844 AN XY: 134154

Gnomad AFR exome AF: 0.000990

Gnomad AMR exome AF: 0.00196

Gnomad ASJ exome AF: 0.00634

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00209

Gnomad FIN exome AF: 0.00879

Gnomad NFE exome AF: 0.00980

Gnomad OTH exome AF: 0.00365

GnomAD4 exome AF: 0.00743 AC: 10819 AN: 1456588 Hom.: 59 Cov.: 31 AF XY: 0.00748 AC XY: 5414 AN XY: 723740

Gnomad4 AFR exome AF: 0.000899

Gnomad4 AMR exome AF: 0.00227

Gnomad4 ASJ exome AF: 0.00676

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00227

Gnomad4 FIN exome AF: 0.00865

Gnomad4 NFE exome AF: 0.00859

Gnomad4 OTH exome AF: 0.00552

GnomAD4 genome AF: 0.00553 AC: 841 AN: 152210 Hom.: 7 Cov.: 33 AF XY: 0.00481 AC XY: 358 AN XY: 74410

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00754

Gnomad4 NFE AF: 0.00935

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00777 Hom.: 9

Bravo AF: 0.00473

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00856 AC: 33

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00698 AC: 60

ExAC AF: 0.00621 AC: 754

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00834

EpiControl AF: 0.00724

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	TAS1R1: BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.014	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	D;D
Vest4		0.42
MVP		0.62
MPC		0.78
ClinPred		0.040	T
GERP RS		-2.5
Varity_R		0.44
gMVP		0.34

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: rs41278022; hg19: chr1-6638925; COSMIC: COSV59840986; COSMIC: COSV59840986;