rs1450839

Positions:

• chr12-10996933-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176889.4(TAS2R20):​c.*13T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,574,768 control chromosomes in the GnomAD database, including 110,006 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (8930 hom., cov: 32)
  • Exomes 𝑓: 0.36 (101076 hom.)
• Consequence: TAS2R20 NM_176889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.16

Genes affected

TAS2R20 (HGNC:19109): (taste 2 receptor member 20) This gene encodes a member of the taste receptor two family of class C G-protein coupled receptors. Receptors of this family have a short extracellular N-terminus, seven transmembrane helices, three extracellular loops and three intracellular loops, and an intracellular C-terminus. Members of this family are expressed in a subset of taste receptor cells, where they function in bitter taste reception, as well as in non-gustatory cells including those of the brain, reproductive organs, respiratory system, and gastrointestinal system. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2016]

ENSG00000275778 (HGNC:):

PRH1 (HGNC:9366): (proline rich protein HaeIII subfamily 1) This gene encodes a member of the heterogeneous family of proline-rich salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid and submandibular/sublingual glands. Multiple distinct alleles of this locus including the parotid isoelectric-focusing variant slow (PIF-s), the parotid acidic protein (Pa), and the double band slow (Db-s) isoforms have been characterized. The reference genome encodes the Db-s allele. Certain alleles of this gene are associated with susceptibility to dental caries. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. Co-transcription of this gene with adjacent genes has been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R20	NM_176889.4	c.*13T>C		3_prime_UTR_variant	1/1	ENST00000538986.2	NP_795370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R20	ENST00000538986	c.*13T>C		3_prime_UTR_variant	1/1		NM_176889.4	ENSP00000441624.1
ENSG00000275778	ENST00000703543.1	c.-125-23212T>C		intron_variant				ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46320 AN: 151838 Hom.: 8928 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.360

GnomAD3 exomes AF: 0.411 AC: 94876 AN: 230902 Hom.: 22475 AF XY: 0.425 AC XY: 52960 AN XY: 124686

Gnomad AFR exome AF: 0.0974

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.521

Gnomad EAS exome AF: 0.751

Gnomad SAS exome AF: 0.629

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.360 AC: 511509 AN: 1422814 Hom.: 101076 Cov.: 31 AF XY: 0.368 AC XY: 259113 AN XY: 703558

Gnomad4 AFR exome AF: 0.0966

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.616

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.305 AC: 46331 AN: 151954 Hom.: 8930 Cov.: 32 AF XY: 0.315 AC XY: 23401 AN XY: 74256

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.363

Alfa AF: 0.347 Hom.: 4106

Bravo AF: 0.301

Asia WGS AF: 0.608 AC: 2109 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1450839; hg19: chr12-11149532; COSMIC: COSV67854936;