1-6575171-A-G

Variant names:

• chr1-6575171-A-G
• rs10864628
• NM_138697.4:c.1039A>G

Variant summary

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

The NM_138697.4(TAS1R1):​c.1039A>G​(p.Lys347Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,595,622 control chromosomes in the GnomAD database, including 779,265 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.93 (66755 hom., cov: 36)
  • Exomes 𝑓: 0.99 (712510 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 26 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 (MetaRNN=1.1004017E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.1039A>G	p.Lys347Glu	missense_variant	Exon 3 of 6	ENST00000333172.11	NP_619642.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.1039A>G	p.Lys347Glu	missense_variant	Exon 3 of 6	1	NM_138697.4	ENSP00000331867.6
TAS1R1	ENST00000415267.1	c.274-1244A>G		intron_variant	Intron 1 of 3	1		ENSP00000408448.1
TAS1R1	ENST00000411823.5	c.814A>G	p.Lys272Glu	missense_variant	Exon 2 of 3	2		ENSP00000414166.1
TAS1R1	ENST00000351136.7	c.499-1244A>G		intron_variant	Intron 2 of 4	2		ENSP00000312558.5

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141583 AN: 152234 Hom.: 66718 Cov.: 36

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.950

GnomAD2 exomes AF: 0.981 AC: 229137 AN: 233682 AF XY: 0.986

Gnomad AFR exome AF: 0.750

Gnomad AMR exome AF: 0.988

Gnomad ASJ exome AF: 0.999

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.990

GnomAD4 exome AF: 0.993 AC: 1433087 AN: 1443270 Hom.: 712510 Cov.: 88 AF XY: 0.994 AC XY: 713470 AN XY: 717832

African (AFR) AF: 0.754 AC: 24415 AN: 32402

American (AMR) AF: 0.986 AC: 39813 AN: 40368

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 24607 AN: 24634

East Asian (EAS) AF: 1.00 AC: 39642 AN: 39642

South Asian (SAS) AF: 0.999 AC: 83392 AN: 83460

European-Finnish (FIN) AF: 1.00 AC: 52658 AN: 52658

Middle Eastern (MID) AF: 0.990 AC: 5592 AN: 5646

European-Non Finnish (NFE) AF: 1.00 AC: 1104443 AN: 1104976

Other (OTH) AF: 0.984 AC: 58525 AN: 59484

GnomAD4 genome AF: 0.930 AC: 141675 AN: 152352 Hom.: 66755 Cov.: 36 AF XY: 0.932 AC XY: 69445 AN XY: 74498

African (AFR) AF: 0.756 AC: 31441 AN: 41566

American (AMR) AF: 0.975 AC: 14928 AN: 15312

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.999 AC: 4825 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67981 AN: 68030

Other (OTH) AF: 0.951 AC: 2012 AN: 2116

Alfa AF: 0.975 Hom.: 136496

Bravo AF: 0.920

TwinsUK AF: 0.999 AC: 3706

ALSPAC AF: 0.999 AC: 3852

ESP6500AA AF: 0.764 AC: 3368

ESP6500EA AF: 0.999 AC: 8594

ExAC AF: 0.977 AC: 118579

Asia WGS AF: 0.985 AC: 3427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	2.0
DANN	Benign	0.34
DEOGEN2	Benign	0.058	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.059	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.13
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.22
Sift	Benign	0.99	T
Sift4G	Benign	0.74	T
Polyphen		0.017	B
Vest4		0.031
MPC		0.23
ClinPred		0.0089	T
GERP RS		-0.46
Varity_R		0.078
gMVP		0.31
Mutation Taster		=99/1	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: rs10864628; hg19: chr1-6635231; COSMIC: COSV59840357; COSMIC: COSV59840357;