rs4763235

Variant names:

• chr12-11022815-C-G
• rs4763235
• ENST00000536668.2:n.109+11967G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-11022815-C-G
• chr12-11022815-C-T

Variant summary

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

The ENST00000536668.2(ENSG00000275778):​n.109+11967G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,020 control chromosomes in the GnomAD database, including 8,245 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 0.29 (8245 hom., cov: 33)
• Consequence: ENSG00000275778 ENST00000536668.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 15 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]

TAS2R19 (HGNC:19108): (taste 2 receptor member 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and sensory perception of taste. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R19	NM_176888.2	c.-244G>C		upstream_gene_variant		ENST00000390673.2	NP_795369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000275778	ENST00000536668.2	n.109+11967G>C		intron_variant	Intron 3 of 9	5		ENSP00000482961.1
TAS2R19	ENST00000390673.2	c.-244G>C		upstream_gene_variant		6	NM_176888.2	ENSP00000375091.2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44008 AN: 151902 Hom.: 8240 Cov.: 33

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.290 AC: 44021 AN: 152020 Hom.: 8245 Cov.: 33 AF XY: 0.300 AC XY: 22256 AN XY: 74296

African (AFR) AF: 0.0914 AC: 3794 AN: 41526

American (AMR) AF: 0.376 AC: 5733 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1725 AN: 3466

East Asian (EAS) AF: 0.738 AC: 3811 AN: 5166

South Asian (SAS) AF: 0.592 AC: 2853 AN: 4820

European-Finnish (FIN) AF: 0.326 AC: 3438 AN: 10540

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21610 AN: 67928

Other (OTH) AF: 0.345 AC: 727 AN: 2110

Alfa AF: 0.281 Hom.: 901

Bravo AF: 0.285

Asia WGS AF: 0.598 AC: 2071 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.090
DANN	Benign	0.21
PhyloP100		-1.3
PromoterAI		0.00040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4763235; hg19: chr12-11175414;