rs3916060

Variant names:

• chr12-10940474-T-C
• rs3916060
• ENST00000536668.2:n.176+33181A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000536668.2(ENSG00000275778):​n.176+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: ENSG00000275778 ENST00000536668.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 3 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=-0.9).
• 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 rank	MANE	Protein	UniProt
PRH1	NM_001291315.2	c.103+33181A>G		intron_variant	Intron 3 of 5		NP_001278244.1
PRH1	NM_001291314.2	c.-59+33181A>G		intron_variant	Intron 3 of 6		NP_001278243.1
PRH1-TAS2R14	NM_001316893.2	c.208-1897A>G		intron_variant	Intron 4 of 4		NP_001303822.1
PRH1-PRR4	NR_037918.2	n.544+33181A>G		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000275778	ENST00000536668.2	n.176+33181A>G		intron_variant	Intron 4 of 9	5		ENSP00000482961.1

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

African (AFR) AF: 0.0207 AC: 861 AN: 41584

American (AMR) AF: 0.120 AC: 1839 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3472

East Asian (EAS) AF: 0.246 AC: 1273 AN: 5178

South Asian (SAS) AF: 0.244 AC: 1177 AN: 4826

European-Finnish (FIN) AF: 0.0789 AC: 837 AN: 10608

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0500 AC: 3404 AN: 68012

Other (OTH) AF: 0.0767 AC: 162 AN: 2112

Alfa AF: 0.0574 Hom.: 264

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
PhyloP100		-0.15

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: rs3916060; hg19: chr12-11093073;