12-10991202-C-T

Variant names:

• chr12-10991202-C-T
• rs10845271
• ENST00000536668.2:n.110-17481G>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.37-17481G>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 NM_001291315.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 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.37-17481G>A		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-125-17481G>A		intron	N/A	NP_001278243.1	A0A087WV42
	PRH1-TAS2R14	NM_001316893.2		c.141-17481G>A		intron	N/A	NP_001303822.1	Q6ZW62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000275778	ENST00000536668.2	TSL:5	n.110-17481G>A		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-125-17481G>A		intron	N/A	ENSP00000515364.1	A0A087WYT0
	PRR4	ENST00000535024.7	TSL:5	c.37-17481G>A		intron	N/A	ENSP00000481571.3	A0A087WY73

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

African (AFR) AF: 0.107 AC: 4419 AN: 41446

American (AMR) AF: 0.394 AC: 6016 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1835 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3812 AN: 5176

South Asian (SAS) AF: 0.621 AC: 2990 AN: 4816

European-Finnish (FIN) AF: 0.329 AC: 3460 AN: 10516

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22674 AN: 67888

Other (OTH) AF: 0.364 AC: 769 AN: 2110

Alfa AF: 0.328 Hom.: 10892

Bravo AF: 0.301

Asia WGS AF: 0.607 AC: 2105 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.41
PhyloP100		-0.17

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: rs10845271; hg19: chr12-11143801;