12-10829813-C-G

Variant names:

• chr12-10829813-C-G
• rs4763216
• ENST00000538332.2:c.*19-4620G>C

Variant summary

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

The ENST00000538332.2(PRH1):​c.*19-4620G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,944 control chromosomes in the GnomAD database, including 21,629 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 0.50 (21629 hom., cov: 32)
• Consequence: PRH1 ENST00000538332.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 4 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRH1	ENST00000538332.2	c.*19-4620G>C		intron_variant	Intron 1 of 1	5		ENSP00000481761.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75989 AN: 151824 Hom.: 21644 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.500 AC: 75977 AN: 151944 Hom.: 21629 Cov.: 32 AF XY: 0.507 AC XY: 37646 AN XY: 74244

African (AFR) AF: 0.211 AC: 8736 AN: 41412

American (AMR) AF: 0.568 AC: 8671 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2355 AN: 3468

East Asian (EAS) AF: 0.661 AC: 3412 AN: 5160

South Asian (SAS) AF: 0.584 AC: 2812 AN: 4818

European-Finnish (FIN) AF: 0.686 AC: 7238 AN: 10550

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40659 AN: 67956

Other (OTH) AF: 0.535 AC: 1129 AN: 2112

Alfa AF: 0.418 Hom.: 1363

Bravo AF: 0.478

Asia WGS AF: 0.585 AC: 2029 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.47
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4763216; hg19: chr12-10982412;