rs11610105

Positions:

• chr12-10936382-G-A

Variant summary

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

The ENST00000703543.1(ENSG00000275778):​c.-59+37273C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,974 control chromosomes in the GnomAD database, including 5,395 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 0.26 (5395 hom., cov: 32)
• Consequence: ENST00000703543.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

Genes affected

(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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRH1-PRR4	NR_037918.2	n.544+37273C>T		intron_variant, non_coding_transcript_variant
PRH1	NM_001291314.2	c.-59+37273C>T		intron_variant
PRH1	NM_001291315.2	c.103+37273C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000703543.1	c.-59+37273C>T		intron_variant				P1
PRH1	ENST00000536086.2	n.89+37273C>T		intron_variant, non_coding_transcript_variant		5
PRH1	ENST00000541977.5	n.359+37273C>T		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000546317.1	n.52+37273C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40083 AN: 151856 Hom.: 5390 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.264 AC: 40110 AN: 151974 Hom.: 5395 Cov.: 32 AF XY: 0.265 AC XY: 19703 AN XY: 74284

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.255

Alfa AF: 0.279 Hom.: 1591

Bravo AF: 0.262

Asia WGS AF: 0.262 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.39

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: rs11610105; hg19: chr12-11088981;