1-6576401-C-T

Variant names:

• chr1-6576401-C-T
• rs17492553
• NM_138697.4:c.1261-14C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138697.4(TAS1R1):​c.1261-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,613,302 control chromosomes in the GnomAD database, including 200,386 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 0.44 (15837 hom., cov: 32)
  • Exomes 𝑓: 0.50 (184549 hom.)
• Consequence: TAS1R1 NM_138697.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138697.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	NM_138697.4	MANE Select	c.1261-14C>T		intron	N/A	NP_619642.2
	TAS1R1	NM_177540.3		c.499-14C>T		intron	N/A	NP_803884.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	ENST00000333172.11	TSL:1 MANE Select	c.1261-14C>T		intron	N/A	ENSP00000331867.6
	TAS1R1	ENST00000415267.1	TSL:1	c.274-14C>T		intron	N/A	ENSP00000408448.1
	TAS1R1	ENST00000351136.7	TSL:2	c.499-14C>T		intron	N/A	ENSP00000312558.5

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67161 AN: 151902 Hom.: 15831 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.427

GnomAD2 exomes AF: 0.482 AC: 121163 AN: 251356 AF XY: 0.478

Gnomad AFR exome AF: 0.277

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.471

Gnomad EAS exome AF: 0.335

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.512

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.498 AC: 728383 AN: 1461282 Hom.: 184549 Cov.: 38 AF XY: 0.496 AC XY: 360582 AN XY: 726946

African (AFR) AF: 0.269 AC: 9012 AN: 33464

American (AMR) AF: 0.551 AC: 24630 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 12208 AN: 26134

East Asian (EAS) AF: 0.362 AC: 14366 AN: 39696

South Asian (SAS) AF: 0.400 AC: 34470 AN: 86246

European-Finnish (FIN) AF: 0.587 AC: 31326 AN: 53386

Middle Eastern (MID) AF: 0.374 AC: 2158 AN: 5764

European-Non Finnish (NFE) AF: 0.514 AC: 571853 AN: 1111500

Other (OTH) AF: 0.470 AC: 28360 AN: 60374

GnomAD4 genome AF: 0.442 AC: 67186 AN: 152020 Hom.: 15837 Cov.: 32 AF XY: 0.443 AC XY: 32944 AN XY: 74312

African (AFR) AF: 0.278 AC: 11520 AN: 41458

American (AMR) AF: 0.485 AC: 7407 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1676 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1741 AN: 5156

South Asian (SAS) AF: 0.382 AC: 1842 AN: 4820

European-Finnish (FIN) AF: 0.600 AC: 6347 AN: 10570

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.518 AC: 35185 AN: 67950

Other (OTH) AF: 0.425 AC: 898 AN: 2112

Alfa AF: 0.396 Hom.: 1936

Bravo AF: 0.430

Asia WGS AF: 0.351 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.69
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17492553; hg19: chr1-6636461; COSMIC: COSV59839543; COSMIC: COSV59839543;