chr12-11035541-A-G

Position:

• chr12-11035541-A-G

Variant summary

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

The NM_001316893.2(PRH1-TAS2R14):​c.37-656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,922 control chromosomes in the GnomAD database, including 15,447 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 0.44 (15447 hom., cov: 32)
• Consequence: PRH1-TAS2R14 NM_001316893.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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 (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRH1-TAS2R14	NM_001316893.2	c.37-656T>C		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.374-656T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000703543.1	c.-126+11479T>C		intron_variant				ENSP00000515364	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66619 AN: 151804 Hom.: 15447 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.439 AC: 66633 AN: 151922 Hom.: 15447 Cov.: 32 AF XY: 0.438 AC XY: 32507 AN XY: 74266

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.403

Alfa AF: 0.471 Hom.: 23846

Bravo AF: 0.424

Asia WGS AF: 0.285 AC: 991 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.53

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: rs7297949; hg19: chr12-11188140;