12-11010392-A-G

Variant names:

• chr12-11010392-A-G
• rs4763606
• ENST00000536668.2:n.109+24390T>C

Variant summary

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

The ENST00000536668.2(ENSG00000275778):​n.109+24390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,714 control chromosomes in the GnomAD database, including 8,883 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 0.30 (8883 hom., cov: 32)
• Consequence: ENSG00000275778 ENST00000536668.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRH1	NM_001291315.2	c.36+36628T>C		intron_variant	Intron 2 of 5		NP_001278244.1
PRH1	NM_001291314.2	c.-126+36628T>C		intron_variant	Intron 2 of 6		NP_001278243.1
PRH1-TAS2R14	NM_001316893.2	c.140+24390T>C		intron_variant	Intron 3 of 4		NP_001303822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000275778	ENST00000536668.2	n.109+24390T>C		intron_variant	Intron 3 of 9	5		ENSP00000482961.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46156 AN: 151596 Hom.: 8879 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.304 AC: 46169 AN: 151714 Hom.: 8883 Cov.: 32 AF XY: 0.314 AC XY: 23302 AN XY: 74134

African (AFR) AF: 0.106 AC: 4393 AN: 41510

American (AMR) AF: 0.393 AC: 5983 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1827 AN: 3460

East Asian (EAS) AF: 0.736 AC: 3786 AN: 5146

South Asian (SAS) AF: 0.622 AC: 2997 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3461 AN: 10538

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22590 AN: 67728

Other (OTH) AF: 0.365 AC: 767 AN: 2102

Alfa AF: 0.331 Hom.: 3174

Bravo AF: 0.301

Asia WGS AF: 0.612 AC: 2117 AN: 3468

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	0.50
PhyloP100		-2.1

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: rs4763606; hg19: chr12-11162991;