rs41278020

Positions:

• chr1-6571046-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000333172.11(TAS1R1):​c.329C>T​(p.Ala110Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,614,170 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (14 hom., cov: 33)
  • Exomes 𝑓: 0.016 (256 hom.)
• Consequence: TAS1R1 ENST00000333172.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007791668).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0122 (1860/152306) while in subpopulation NFE AF= 0.0193 (1310/68024). AF 95% confidence interval is 0.0184. There are 14 homozygotes in gnomad4. There are 840 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.329C>T	p.Ala110Val	missense_variant	2/6	ENST00000333172.11	NP_619642.2
LOC107984912	XR_002958250.1	n.88-1063G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.329C>T	p.Ala110Val	missense_variant	2/6	1	NM_138697.4	ENSP00000331867	P1
TAS1R1	ENST00000415267.1	c.107C>T	p.Ala36Val	missense_variant	1/4	1		ENSP00000408448
TAS1R1	ENST00000351136.7	c.329C>T	p.Ala110Val	missense_variant	2/5	2		ENSP00000312558
TAS1R1	ENST00000411823.5	c.107C>T	p.Ala36Val	missense_variant	1/3	2		ENSP00000414166

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1861 AN: 152188 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.0118 AC: 2960 AN: 251410 Hom.: 31 AF XY: 0.0122 AC XY: 1661 AN XY: 135878

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00943

Gnomad ASJ exome AF: 0.00626

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0116

Gnomad FIN exome AF: 0.00356

Gnomad NFE exome AF: 0.0177

Gnomad OTH exome AF: 0.0140

GnomAD4 exome AF: 0.0163 AC: 23856 AN: 1461864 Hom.: 256 Cov.: 32 AF XY: 0.0163 AC XY: 11879 AN XY: 727238

Gnomad4 AFR exome AF: 0.00212

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.00578

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.00438

Gnomad4 NFE exome AF: 0.0189

Gnomad4 OTH exome AF: 0.0149

GnomAD4 genome AF: 0.0122 AC: 1860 AN: 152306 Hom.: 14 Cov.: 33 AF XY: 0.0113 AC XY: 840 AN XY: 74472

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.0193

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0163 Hom.: 37

Bravo AF: 0.0122

TwinsUK AF: 0.0143 AC: 53

ALSPAC AF: 0.0163 AC: 63

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.0164 AC: 141

ExAC AF: 0.0118 AC: 1435

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0182

EpiControl AF: 0.0198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.87	D;D
MetaRNN	Benign	0.0078	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	0.66	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.29
Sift	Benign	0.14	T;T
Sift4G	Benign	0.34	T;T
Polyphen		1.0	D;D
Vest4		0.43
MPC		0.54
ClinPred		0.023	T
GERP RS		5.1
Varity_R		0.22
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs41278020; hg19: chr1-6631106;