1-6575199-C-G

Position:

• chr1-6575199-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_138697.4(TAS1R1):​c.1067C>G​(p.Ser356Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,611,470 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.0020 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (10 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008608997).
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.1067C>G	p.Ser356Cys	missense_variant	3/6	ENST00000333172.11	NP_619642.2
LOC107984912	XR_002958250.1	n.87+4148G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.1067C>G	p.Ser356Cys	missense_variant	3/6	1	NM_138697.4	ENSP00000331867	P1
TAS1R1	ENST00000415267.1	c.276-1216C>G		intron_variant		1		ENSP00000408448
TAS1R1	ENST00000411823.5	c.845C>G	p.Ser282Cys	missense_variant	2/3	2		ENSP00000414166
TAS1R1	ENST00000351136.7	c.499-1216C>G		intron_variant		2		ENSP00000312558

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 308 AN: 152242 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00335

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00229 AC: 567 AN: 247914 Hom.: 2 AF XY: 0.00235 AC XY: 316 AN XY: 134198

Gnomad AFR exome AF: 0.000619

Gnomad AMR exome AF: 0.00320

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00165

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.00317

Gnomad OTH exome AF: 0.00677

GnomAD4 exome AF: 0.00310 AC: 4523 AN: 1459110 Hom.: 10 Cov.: 36 AF XY: 0.00315 AC XY: 2286 AN XY: 725856

Gnomad4 AFR exome AF: 0.000659

Gnomad4 AMR exome AF: 0.00313

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00177

Gnomad4 FIN exome AF: 0.000170

Gnomad4 NFE exome AF: 0.00363

Gnomad4 OTH exome AF: 0.00236

GnomAD4 genome AF: 0.00202 AC: 308 AN: 152360 Hom.: 1 Cov.: 33 AF XY: 0.00179 AC XY: 133 AN XY: 74496

Gnomad4 AFR AF: 0.000697

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00335

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00297 Hom.: 0

Bravo AF: 0.00220

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00349 AC: 30

ExAC AF: 0.00229 AC: 278

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.34
Sift	Benign	0.036	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.39
MVP		0.63
MPC		0.64
ClinPred		0.022	T
GERP RS		4.5
Varity_R		0.26
gMVP		0.35

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: rs41307749; hg19: chr1-6635259;