rs34836514

chr12-11054586-G-Achr12-11054586-G-Cchr12-11054586-G-T

Variant summary

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

The NM_001316893.2(PRH1-TAS2R14):c.-133-7398C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 149,336 control chromosomes in the GnomAD database, including 3,998 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 0.22 (3998 hom., cov: 32)
• Consequence: PRH1-TAS2R14 NM_001316893.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

Genes affected

PRH1-TAS2R14 (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]

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRH1-TAS2R14	NM_001316893.2	c.-133-7398C>T		intron_variant
PRH1-PRR4	NR_037918.2	n.205-7398C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R14	ENST00000381852.4	n.153-7398C>T		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000541977.5	n.124-7398C>T		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000546265.1	n.359-7398C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32174 AN: 149220 Hom.: 4001 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0570

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.215 AC: 32174 AN: 149336 Hom.: 3998 Cov.: 32 AF XY: 0.213 AC XY: 15522 AN XY: 72802

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.0564

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.195

Alfa AF: 0.215 Hom.: 1306

Bravo AF: 0.202

Asia WGS AF: 0.0490 AC: 172 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.0
Dann	Benign	0.38

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: rs34836514; hg19: chr12-11207185;