chr12-10936382-G-A

Variant names:

• chr12-10936382-G-A
• rs11610105
• ENST00000536668.2:n.176+37273C>T

Variant summary

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

The ENST00000536668.2(ENSG00000275778):​n.176+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: ENSG00000275778 ENST00000536668.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRH1	NM_001291315.2	c.103+37273C>T		intron_variant	Intron 3 of 5		NP_001278244.1
PRH1	NM_001291314.2	c.-59+37273C>T		intron_variant	Intron 3 of 6		NP_001278243.1
PRH1-PRR4	NR_037918.2	n.544+37273C>T		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000275778	ENST00000536668.2	n.176+37273C>T		intron_variant	Intron 4 of 9	5		ENSP00000482961.1

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

African (AFR) AF: 0.251 AC: 10415 AN: 41444

American (AMR) AF: 0.286 AC: 4363 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 782 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1189 AN: 5176

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4814

European-Finnish (FIN) AF: 0.278 AC: 2933 AN: 10544

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18544 AN: 67958

Other (OTH) AF: 0.255 AC: 538 AN: 2108

Alfa AF: 0.276 Hom.: 2046

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
PhyloP100		-0.61

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: rs11610105; hg19: chr12-11088981;