chr1-6574673-C-G

Position:

• chr1-6574673-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_138697.4(TAS1R1):​c.541C>G​(p.Gln181Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,264 control chromosomes in the GnomAD database, including 20 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 0.0062 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (6 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.49

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011758864).
• BP6: Variant 1-6574673-C-G is Benign according to our data. Variant chr1-6574673-C-G is described in ClinVar as [Benign]. Clinvar id is 709202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00618 (942/152354) while in subpopulation AFR AF= 0.0214 (890/41586). AF 95% confidence interval is 0.0202. There are 14 homozygotes in gnomad4. There are 448 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.541C>G	p.Gln181Glu	missense_variant	3/6	ENST00000333172.11	NP_619642.2
LOC107984912	XR_002958250.1	n.87+4674G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.541C>G	p.Gln181Glu	missense_variant	3/6	1	NM_138697.4	ENSP00000331867	P1
TAS1R1	ENST00000415267.1	c.276-1742C>G		intron_variant		1		ENSP00000408448
TAS1R1	ENST00000411823.5	c.319C>G	p.Gln107Glu	missense_variant	2/3	2		ENSP00000414166
TAS1R1	ENST00000351136.7	c.499-1742C>G		intron_variant		2		ENSP00000312558

Frequencies

GnomAD3 genomes AF: 0.00617 AC: 939 AN: 152236 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

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: 0.0000735

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00146 AC: 365 AN: 250658 Hom.: 2 AF XY: 0.00108 AC XY: 146 AN XY: 135442

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.000898

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: 0.0000177

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000591 AC: 863 AN: 1460910 Hom.: 6 Cov.: 31 AF XY: 0.000506 AC XY: 368 AN XY: 726616

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000900

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00618 AC: 942 AN: 152354 Hom.: 14 Cov.: 32 AF XY: 0.00601 AC XY: 448 AN XY: 74490

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.000345 Hom.: 0

Bravo AF: 0.00697

ESP6500AA AF: 0.0213 AC: 94

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00185 AC: 225

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 09, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.0
DANN	Benign	0.86
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.95	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.15
Sift	Benign	0.27	T
Sift4G	Benign	0.28	T
Polyphen		0.062	B
Vest4		0.067
MVP		0.60
MPC		0.22
ClinPred		0.0047	T
GERP RS		-2.5
Varity_R		0.13
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs74049682; hg19: chr1-6634733;