12-10991202-C-T

Position:

• chr12-10991202-C-T

Variant summary

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

The NM_001316893.2(PRH1-TAS2R14):​c.141-17481G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,906 control chromosomes in the GnomAD database, including 8,922 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 0.31 (8922 hom., cov: 32)
• Consequence: PRH1-TAS2R14 NM_001316893.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

PRH1-TAS2R14 (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]

TAS2R14 (HGNC:14920): (taste 2 receptor member 14) This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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
PRH1-TAS2R14	NM_001316893.2	c.141-17481G>A		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.478-17481G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000703543.1	c.-125-17481G>A		intron_variant				ENSP00000515364	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46330 AN: 151788 Hom.: 8919 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.361

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.305 AC: 46343 AN: 151906 Hom.: 8922 Cov.: 32 AF XY: 0.315 AC XY: 23402 AN XY: 74248

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.364

Alfa AF: 0.356 Hom.: 7629

Bravo AF: 0.301

Asia WGS AF: 0.607 AC: 2105 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.41

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: rs10845271; hg19: chr12-11143801;