chr1-6571046-C-T

Variant names:

• chr1-6571046-C-T
• rs41278020
• NM_138697.4:c.329C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_138697.4(TAS1R1):​c.329C>T​(p.Ala110Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,614,170 control chromosomes in the GnomAD database, including 270 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 0.012 (14 hom., cov: 33)
  • Exomes 𝑓: 0.016 (256 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 18 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=0.007791668).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0122 (1860/152306) while in subpopulation NFE AF = 0.0193 (1310/68024). AF 95% confidence interval is 0.0184. There are 14 homozygotes in GnomAd4. There are 840 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	NM_138697.4	MANE Select	c.329C>T	p.Ala110Val	missense	Exon 2 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.329C>T	p.Ala110Val	missense	Exon 2 of 5	NP_803884.1	Q7RTX1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	ENST00000333172.11	TSL:1 MANE Select	c.329C>T	p.Ala110Val	missense	Exon 2 of 6	ENSP00000331867.6	Q7RTX1-1
	TAS1R1	ENST00000415267.1	TSL:1	c.104C>T	p.Ala35Val	missense	Exon 1 of 4	ENSP00000408448.1	H0Y6X0
	TAS1R1	ENST00000351136.7	TSL:2	c.329C>T	p.Ala110Val	missense	Exon 2 of 5	ENSP00000312558.5	Q7RTX1-2

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1861 AN: 152188 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.0118 AC: 2960 AN: 251410 AF XY: 0.0122

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00943

Gnomad ASJ exome AF: 0.00626

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00356

Gnomad NFE exome AF: 0.0177

Gnomad OTH exome AF: 0.0140

GnomAD4 exome AF: 0.0163 AC: 23856 AN: 1461864 Hom.: 256 Cov.: 32 AF XY: 0.0163 AC XY: 11879 AN XY: 727238

African (AFR) AF: 0.00212 AC: 71 AN: 33480

American (AMR) AF: 0.0102 AC: 456 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00578 AC: 151 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0109 AC: 936 AN: 86254

European-Finnish (FIN) AF: 0.00438 AC: 234 AN: 53420

Middle Eastern (MID) AF: 0.00902 AC: 52 AN: 5766

European-Non Finnish (NFE) AF: 0.0189 AC: 21053 AN: 1112006

Other (OTH) AF: 0.0149 AC: 902 AN: 60392

GnomAD4 genome AF: 0.0122 AC: 1860 AN: 152306 Hom.: 14 Cov.: 33 AF XY: 0.0113 AC XY: 840 AN XY: 74472

African (AFR) AF: 0.00289 AC: 120 AN: 41562

American (AMR) AF: 0.0172 AC: 263 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4828

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10622

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0193 AC: 1310 AN: 68024

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0158 Hom.: 53

Bravo AF: 0.0122

TwinsUK AF: 0.0143 AC: 53

ALSPAC AF: 0.0163 AC: 63

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.0164 AC: 141

ExAC AF: 0.0118 AC: 1435

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0182

EpiControl AF: 0.0198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.29
Sift	Benign	0.14	T
Sift4G	Benign	0.34	T
Polyphen		1.0	D
Vest4		0.43
MPC		0.54
ClinPred		0.023	T
GERP RS		5.1
PromoterAI		-0.0018	Neutral
Varity_R		0.22
gMVP		0.29
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs41278020; hg19: chr1-6631106;