chr12-11022815-C-G

Position:

• chr12-11022815-C-G

Variant summary

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

The NM_001316893.2(PRH1-TAS2R14):​c.140+11967G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,020 control chromosomes in the GnomAD database, including 8,245 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 0.29 (8245 hom., cov: 33)
• Consequence: PRH1-TAS2R14 NM_001316893.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRH1-TAS2R14	NM_001316893.2	c.140+11967G>C		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.477+11967G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000703543.1	c.-126+24205G>C		intron_variant				ENSP00000515364	P1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44008 AN: 151902 Hom.: 8240 Cov.: 33

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.290 AC: 44021 AN: 152020 Hom.: 8245 Cov.: 33 AF XY: 0.300 AC XY: 22256 AN XY: 74296

Gnomad4 AFR AF: 0.0914

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.345

Alfa AF: 0.281 Hom.: 901

Bravo AF: 0.285

Asia WGS AF: 0.598 AC: 2071 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.090
DANN	Benign	0.21

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: rs4763235; hg19: chr12-11175414;