chr1-6570918-C-T

Variant names:

• chr1-6570918-C-T
• rs61746701
• NM_138697.4:c.201C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_138697.4(TAS1R1):​c.201C>T​(p.Ser67Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,599,856 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (24 hom.)
• Consequence: TAS1R1 NM_138697.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0140
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-6570918-C-T is Benign according to our data. Variant chr1-6570918-C-T is described in ClinVar as Benign. ClinVar VariationId is 775496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.014 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00834 (1270/152312) while in subpopulation AFR AF = 0.0287 (1193/41570). AF 95% confidence interval is 0.0273. There are 15 homozygotes in GnomAd4. There are 579 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 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.201C>T	p.Ser67Ser	synonymous	Exon 2 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.201C>T	p.Ser67Ser	synonymous	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.201C>T	p.Ser67Ser	synonymous	Exon 2 of 6	ENSP00000331867.6	Q7RTX1-1
	TAS1R1	ENST00000351136.7	TSL:2	c.201C>T	p.Ser67Ser	synonymous	Exon 2 of 5	ENSP00000312558.5	Q7RTX1-2
	TAS1R1	ENST00000415267.1	TSL:1	c.-25C>T		upstream_gene	N/A	ENSP00000408448.1	H0Y6X0

Frequencies

GnomAD3 genomes AF: 0.00833 AC: 1268 AN: 152194 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

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: 0.000118

Gnomad OTH AF: 0.00958

GnomAD2 exomes AF: 0.00263 AC: 623 AN: 236578 AF XY: 0.00202

Gnomad AFR exome AF: 0.0336

Gnomad AMR exome AF: 0.00163

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.000909 AC: 1316 AN: 1447544 Hom.: 24 Cov.: 31 AF XY: 0.000757 AC XY: 544 AN XY: 718770

African (AFR) AF: 0.0310 AC: 1034 AN: 33378

American (AMR) AF: 0.00189 AC: 83 AN: 43966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24632

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.0000362 AC: 3 AN: 82790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52612

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5688

European-Non Finnish (NFE) AF: 0.0000606 AC: 67 AN: 1104944

Other (OTH) AF: 0.00205 AC: 123 AN: 59864

GnomAD4 genome AF: 0.00834 AC: 1270 AN: 152312 Hom.: 15 Cov.: 32 AF XY: 0.00777 AC XY: 579 AN XY: 74472

African (AFR) AF: 0.0287 AC: 1193 AN: 41570

American (AMR) AF: 0.00320 AC: 49 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68030

Other (OTH) AF: 0.00948 AC: 20 AN: 2110

Alfa AF: 0.00484 Hom.: 5

Bravo AF: 0.0102

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
DANN	Benign	0.51
PhyloP100		0.014
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs61746701; hg19: chr1-6630978;