rs3916060

Positions:

• chr12-10940474-T-C
• chr12-10940474-T-G

Variant summary

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

The NM_001291315.2(PRH1):​c.103+33181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 152,300 control chromosomes in the GnomAD database, including 598 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 0.066 (598 hom., cov: 32)
• Consequence: PRH1 NM_001291315.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRH1	NM_001291315.2	c.103+33181A>G		intron_variant			NP_001278244.1
PRH1	NM_001291314.2	c.-59+33181A>G		intron_variant			NP_001278243.1
PRH1-TAS2R14	NM_001316893.2	c.208-1897A>G		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.544+33181A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000275778	ENST00000703543.1	c.-59+33181A>G		intron_variant				ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9973 AN: 152184 Hom.: 599 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0765

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

GnomAD4 genome AF: 0.0655 AC: 9982 AN: 152300 Hom.: 598 Cov.: 32 AF XY: 0.0730 AC XY: 5436 AN XY: 74468

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0767

Alfa AF: 0.0559 Hom.: 156

Bravo AF: 0.0662

Asia WGS AF: 0.231 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.64

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: rs3916060; hg19: chr12-11093073;