1-6563439-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138697.4(TAS1R1):c.192-7470C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,092 control chromosomes in the GnomAD database, including 18,574 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (18574 hom., cov: 33)
• Consequence: TAS1R1 NM_138697.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS1R1	NM_138697.4	c.192-7470C>T		intron_variant		ENST00000333172.11
TAS1R1	NM_177540.3	c.192-7470C>T		intron_variant
TAS1R1	XM_011542206.3	c.192-7470C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS1R1	ENST00000333172.11	c.192-7470C>T		intron_variant		1	NM_138697.4	P1
TAS1R1	ENST00000351136.7	c.192-7470C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69691 AN: 151974 Hom.: 18568 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.458 AC: 69704 AN: 152092 Hom.: 18574 Cov.: 33 AF XY: 0.461 AC XY: 34298 AN XY: 74332

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.497

Alfa AF: 0.548 Hom.: 31708

Bravo AF: 0.451

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.9
Dann	Benign	0.48

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: rs4908563; hg19: chr1-6623499;