rs1031391

Variant names:

• chr12-11126493-C-G
• rs1031391
• NM_001291315.2:c.-134+44929G>C

Variant summary

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

The NM_001291315.2(PRH1):​c.-134+44929G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 133,588 control chromosomes in the GnomAD database, including 13,273 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 0.49 (13273 hom., cov: 30)
• Consequence: PRH1 NM_001291315.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

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]

PRH1-TAS2R14 (HGNC:):

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRH1	NM_001291315.2	c.-134+44929G>C		intron_variant	Intron 1 of 5		NP_001278244.1
PRH1	NM_001291314.2	c.-295+44929G>C		intron_variant	Intron 1 of 6		NP_001278243.1
PRH1-TAS2R14	NM_001316893.2	c.-134+44929G>C		intron_variant	Intron 1 of 4		NP_001303822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000275778	ENST00000535024.6	c.-134+44929G>C		intron_variant	Intron 1 of 4	5		ENSP00000481571.2
TAS2R14	ENST00000381852.4	n.152+44929G>C		intron_variant	Intron 1 of 4	2
ENSG00000275778	ENST00000536668.2	n.-165+44929G>C		intron_variant	Intron 1 of 9	5		ENSP00000482961.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 64842 AN: 133498 Hom.: 13273 Cov.: 30

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.486 AC: 64859 AN: 133588 Hom.: 13273 Cov.: 30 AF XY: 0.483 AC XY: 31698 AN XY: 65580

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.463

Alfa AF: 0.600 Hom.: 2149

Asia WGS AF: 0.299 AC: 1042 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.45

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: rs1031391; hg19: chr12-11279092;