rs34836514

Positions:

• chr12-11054586-G-A
• chr12-11054586-G-C
• chr12-11054586-G-T

Variant summary

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

The NM_001291315.2(PRH1):​c.-133-7398C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 149,336 control chromosomes in the GnomAD database, including 3,998 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 0.22 (3998 hom., cov: 32)
• Consequence: PRH1 NM_001291315.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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]

PRH1-TAS2R14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRH1	NM_001291315.2	c.-133-7398C>T		intron_variant			NP_001278244.1
PRH1	NM_001291314.2	c.-294-7398C>T		intron_variant			NP_001278243.1
PRH1-TAS2R14	NM_001316893.2	c.-133-7398C>T		intron_variant			NP_001303822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000275778	ENST00000535024.6	c.-133-7398C>T		intron_variant		5		ENSP00000481571.2
TAS2R14	ENST00000381852.4	n.153-7398C>T		intron_variant		2
ENSG00000275778	ENST00000536668.2	n.-164-7398C>T		intron_variant		5		ENSP00000482961.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32174 AN: 149220 Hom.: 4001 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0570

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.215 AC: 32174 AN: 149336 Hom.: 3998 Cov.: 32 AF XY: 0.213 AC XY: 15522 AN XY: 72802

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.0564

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.195

Alfa AF: 0.215 Hom.: 1306

Bravo AF: 0.202

Asia WGS AF: 0.0490 AC: 172 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.38

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: rs34836514; hg19: chr12-11207185;