rs10845278

Variant names:

• chr12-10995543-T-C
• rs10845278
• ENST00000536668.2:n.110-21822A>G

Variant summary

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

The ENST00000536668.2(ENSG00000275778):​n.110-21822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,136 control chromosomes in the GnomAD database, including 4,092 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 0.21 (4092 hom., cov: 32)
• Consequence: ENSG00000275778 ENST00000536668.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000536668.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRH1	NM_001291315.2		c.37-21822A>G		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-125-21822A>G		intron	N/A	NP_001278243.1
	PRH1-TAS2R14	NM_001316893.2		c.141-21822A>G		intron	N/A	NP_001303822.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000275778	ENST00000536668.2	TSL:5	n.110-21822A>G		intron	N/A	ENSP00000482961.1
	PRH1	ENST00000703543.1		c.-125-21822A>G		intron	N/A	ENSP00000515364.1
	PRR4	ENST00000535024.7	TSL:5	c.37-21822A>G		intron	N/A	ENSP00000481571.3

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32454 AN: 152018 Hom.: 4094 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.213 AC: 32455 AN: 152136 Hom.: 4092 Cov.: 32 AF XY: 0.211 AC XY: 15666 AN XY: 74374

African (AFR) AF: 0.132 AC: 5498 AN: 41534

American (AMR) AF: 0.210 AC: 3205 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 507 AN: 3468

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5184

South Asian (SAS) AF: 0.0537 AC: 259 AN: 4824

European-Finnish (FIN) AF: 0.328 AC: 3465 AN: 10570

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18609 AN: 67974

Other (OTH) AF: 0.192 AC: 404 AN: 2108

Alfa AF: 0.147 Hom.: 293

Bravo AF: 0.203

Asia WGS AF: 0.0480 AC: 168 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.69
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10845278; hg19: chr12-11148142;