12-11012152-G-A

Variant names:

• chr12-11012152-G-A
• rs7315843
• ENST00000536668.2:n.109+22630C>T

Variant summary

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

The ENST00000536668.2(ENSG00000275778):​n.109+22630C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,142 control chromosomes in the GnomAD database, including 51,727 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 0.82 (51727 hom., cov: 33)
• Consequence: ENSG00000275778 ENST00000536668.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.22
• Publications: 9 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000536668.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRH1	NM_001291315.2		c.36+34868C>T		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-126+34868C>T		intron	N/A	NP_001278243.1
	PRH1-TAS2R14	NM_001316893.2		c.140+22630C>T		intron	N/A	NP_001303822.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000275778	ENST00000536668.2	TSL:5	n.109+22630C>T		intron	N/A	ENSP00000482961.1
	PRH1	ENST00000703543.1		c.-126+34868C>T		intron	N/A	ENSP00000515364.1
	PRR4	ENST00000535024.7	TSL:5	c.36+34868C>T		intron	N/A	ENSP00000481571.3

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124965 AN: 152024 Hom.: 51704 Cov.: 33

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.822 AC: 125030 AN: 152142 Hom.: 51727 Cov.: 33 AF XY: 0.828 AC XY: 61582 AN XY: 74378

African (AFR) AF: 0.723 AC: 30007 AN: 41478

American (AMR) AF: 0.862 AC: 13160 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2917 AN: 3472

East Asian (EAS) AF: 0.959 AC: 4958 AN: 5168

South Asian (SAS) AF: 0.863 AC: 4174 AN: 4834

European-Finnish (FIN) AF: 0.925 AC: 9808 AN: 10608

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57231 AN: 67992

Other (OTH) AF: 0.825 AC: 1745 AN: 2114

Alfa AF: 0.836 Hom.: 49132

Bravo AF: 0.813

Asia WGS AF: 0.911 AC: 3156 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.33
PhyloP100		-5.2

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: rs7315843; hg19: chr12-11164751; COSMIC: COSV67857686;