chr1-6574704-A-G

Position:

• chr1-6574704-A-G

Variant summary

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

The ENST00000333172.11(TAS1R1):​c.572A>G​(p.Asn191Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00218 in 1,614,158 control chromosomes in the GnomAD database, including 56 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 0.0078 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (39 hom.)
• Consequence: TAS1R1 ENST00000333172.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.65

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=0.0077606738).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00776 (1182/152284) while in subpopulation EAS AF= 0.0375 (194/5172). AF 95% confidence interval is 0.0332. There are 17 homozygotes in gnomad4. There are 550 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.572A>G	p.Asn191Ser	missense_variant	3/6	ENST00000333172.11	NP_619642.2
LOC107984912	XR_002958250.1	n.87+4643T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.572A>G	p.Asn191Ser	missense_variant	3/6	1	NM_138697.4	ENSP00000331867	P1
TAS1R1	ENST00000415267.1	c.276-1711A>G		intron_variant		1		ENSP00000408448
TAS1R1	ENST00000411823.5	c.350A>G	p.Asn117Ser	missense_variant	2/3	2		ENSP00000414166
TAS1R1	ENST00000351136.7	c.499-1711A>G		intron_variant		2		ENSP00000312558

Frequencies

GnomAD3 genomes AF: 0.00775 AC: 1180 AN: 152164 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00455 AC: 1144 AN: 251362 Hom.: 24 AF XY: 0.00400 AC XY: 543 AN XY: 135856

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0361

Gnomad SAS exome AF: 0.00108

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00160 AC: 2336 AN: 1461874 Hom.: 39 Cov.: 31 AF XY: 0.00148 AC XY: 1077 AN XY: 727240

Gnomad4 AFR exome AF: 0.0190

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0200

Gnomad4 SAS exome AF: 0.00138

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000275

Gnomad4 OTH exome AF: 0.00641

GnomAD4 genome AF: 0.00776 AC: 1182 AN: 152284 Hom.: 17 Cov.: 32 AF XY: 0.00738 AC XY: 550 AN XY: 74478

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0375

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00247 Hom.: 5

Bravo AF: 0.00883

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0238 AC: 105

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00464 AC: 564

Asia WGS AF: 0.0210 AC: 72 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.23
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.4	N
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	2.2	N
REVEL	Uncertain	0.32
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MVP		0.52
MPC		0.13
ClinPred		0.0070	T
GERP RS		4.3
Varity_R		0.090
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs61744700; hg19: chr1-6634764; COSMIC: COSV60227947;