1-6575249-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_138697.4(TAS1R1):c.1117C>A(p.His373Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,613,486 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (17 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.478

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038735569).
• BP6: Variant 1-6575249-C-A is Benign according to our data. Variant chr1-6575249-C-A is described in ClinVar as [Benign]. Clinvar id is 775497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00711 (1083/152368) while in subpopulation AFR AF= 0.0245 (1019/41592). AF 95% confidence interval is 0.0233. There are 10 homozygotes in gnomad4. There are 486 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS1R1	NM_138697.4	c.1117C>A	p.His373Asn	missense_variant	3/6	ENST00000333172.11
LOC107984912	XR_002958250.1	n.87+4098G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS1R1	ENST00000333172.11	c.1117C>A	p.His373Asn	missense_variant	3/6	1	NM_138697.4	P1
TAS1R1	ENST00000415267.1	c.276-1166C>A		intron_variant		1
TAS1R1	ENST00000411823.5	c.895C>A	p.His299Asn	missense_variant	2/3	2
TAS1R1	ENST00000351136.7	c.499-1166C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00710 AC: 1081 AN: 152250 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00217 AC: 543 AN: 249916 Hom.: 12 AF XY: 0.00165 AC XY: 224 AN XY: 135466

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000775 AC: 1132 AN: 1461118 Hom.: 17 Cov.: 34 AF XY: 0.000649 AC XY: 472 AN XY: 726872

Gnomad4 AFR exome AF: 0.0261

Gnomad4 AMR exome AF: 0.00170

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000594

Gnomad4 OTH exome AF: 0.00180

GnomAD4 genome AF: 0.00711 AC: 1083 AN: 152368 Hom.: 10 Cov.: 32 AF XY: 0.00652 AC XY: 486 AN XY: 74510

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00161 Hom.: 5

Bravo AF: 0.00866

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0238 AC: 105

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00251 AC: 305

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	0.23
Dann	Benign	0.50
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.050	N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.099
Sift	Benign	0.36	T
Sift4G	Benign	0.63	T
Polyphen		0.0010	B
Vest4		0.099
MVP		0.42
MPC		0.18
ClinPred		0.0024	T
GERP RS		-1.5
Varity_R		0.089
gMVP		0.13

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: rs115225713; hg19: chr1-6635309;