12-11063716-C-T

Variant names:

• chr12-11063716-C-T
• rs2708377
• ENST00000536668.2:n.-164-16528G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291315.2(PRH1):​c.-133-16528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,910 control chromosomes in the GnomAD database, including 44,716 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 0.75 (44716 hom., cov: 31)
• Consequence: PRH1 NM_001291315.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 17 publications found

Genes affected

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]

PRR4 (HGNC:18020): (proline rich 4) This gene encodes a member of the proline-rich protein family that lacks a conserved repetitive domain. This protein may play a role in protective functions in the eye. Alternative splicing result in multiple transcript variants. Read-through transcription also exists between this gene and the upstream PRH1 (proline-rich protein HaeIII subfamily 1) gene. [provided by RefSeq, Feb 2011]

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291315.2. 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
	PRH1	NM_001291315.2		c.-133-16528G>A		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-294-16528G>A		intron	N/A	NP_001278243.1
	PRH1-TAS2R14	NM_001316893.2		c.-133-16528G>A		intron	N/A	NP_001303822.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000275778	ENST00000536668.2	TSL:5	n.-164-16528G>A		intron	N/A	ENSP00000482961.1
	PRR4	ENST00000535024.7	TSL:5	c.-133-16528G>A		intron	N/A	ENSP00000481571.3
	TAS2R14	ENST00000381852.4	TSL:2	n.153-16528G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113293 AN: 151792 Hom.: 44704 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.746 AC: 113321 AN: 151910 Hom.: 44716 Cov.: 31 AF XY: 0.755 AC XY: 56093 AN XY: 74276

African (AFR) AF: 0.458 AC: 18962 AN: 41364

American (AMR) AF: 0.825 AC: 12571 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2915 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4929 AN: 5158

South Asian (SAS) AF: 0.864 AC: 4165 AN: 4822

European-Finnish (FIN) AF: 0.925 AC: 9795 AN: 10588

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57331 AN: 67958

Other (OTH) AF: 0.771 AC: 1627 AN: 2110

Alfa AF: 0.835 Hom.: 96087

Bravo AF: 0.726

Asia WGS AF: 0.898 AC: 3118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.94
DANN	Benign	0.33
PhyloP100		-2.9

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

Other links and lift over

dbSNP: rs2708377; hg19: chr12-11216315;