rs11612527

Variant names:

• chr12-11028949-T-A
• rs11612527
• ENST00000536668.2:n.109+5833A>T

Variant summary

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

The ENST00000536668.2(ENSG00000275778):​n.109+5833A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 151,856 control chromosomes in the GnomAD database, including 16 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 0.17 (16 hom., cov: 43)
• Consequence: ENSG00000275778 ENST00000536668.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 4 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]

TAS2R14 (HGNC:14920): (taste 2 receptor member 14) This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRH1	NM_001291315.2	c.36+18071A>T		intron_variant	Intron 2 of 5		NP_001278244.1
PRH1	NM_001291314.2	c.-126+18071A>T		intron_variant	Intron 2 of 6		NP_001278243.1
PRH1-TAS2R14	NM_001316893.2	c.140+5833A>T		intron_variant	Intron 3 of 4		NP_001303822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000275778	ENST00000536668.2	n.109+5833A>T		intron_variant	Intron 3 of 9	5		ENSP00000482961.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25784 AN: 151738 Hom.: 16 Cov.: 43

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.170 AC: 25782 AN: 151856 Hom.: 16 Cov.: 43 AF XY: 0.172 AC XY: 12751 AN XY: 74224

African (AFR) AF: 0.0872 AC: 3620 AN: 41502

American (AMR) AF: 0.183 AC: 2783 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 519 AN: 3466

East Asian (EAS) AF: 0.192 AC: 996 AN: 5178

South Asian (SAS) AF: 0.167 AC: 804 AN: 4810

European-Finnish (FIN) AF: 0.234 AC: 2471 AN: 10558

Middle Eastern (MID) AF: 0.159 AC: 46 AN: 290

European-Non Finnish (NFE) AF: 0.208 AC: 14080 AN: 67806

Other (OTH) AF: 0.169 AC: 357 AN: 2110

Alfa AF: 0.196 Hom.: 7

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.79
PhyloP100		-0.045

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: rs11612527; hg19: chr12-11181548;