chr12-10987845-T-C

Position:

• chr12-10987845-T-C

Variant summary

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

The NM_001316893.2(PRH1-TAS2R14):​c.141-14124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,000 control chromosomes in the GnomAD database, including 33,349 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 0.64 (33349 hom., cov: 31)
• Consequence: PRH1-TAS2R14 NM_001316893.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRH1-TAS2R14	NM_001316893.2	c.141-14124A>G		intron_variant
PRH1-PRR4	NR_037918.2	n.478-14124A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000703543.1	c.-125-14124A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96629 AN: 151880 Hom.: 33352 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.636 AC: 96647 AN: 152000 Hom.: 33349 Cov.: 31 AF XY: 0.640 AC XY: 47559 AN XY: 74294

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.676

Alfa AF: 0.545 Hom.: 2777

Bravo AF: 0.622

Asia WGS AF: 0.704 AC: 2448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.52

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: rs6488334; hg19: chr12-11140444;