12-11495484-C-T

Position:

• chr12-11495484-C-T

Variant summary

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

The ENST00000545829.1(PRB2):​n.364+5194G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,062 control chromosomes in the GnomAD database, including 6,755 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 (6755 hom., cov: 32)
• Consequence: PRB2 ENST00000545829.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676

Genes affected

PRB2 (HGNC:9338): (proline rich protein BstNI subfamily 2) This gene encodes a member of the heterogeneous family of basic, proline-rich, human salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid glands. Multiple alleles of this gene exhibiting variations in the length of the tandem repeats, polymorphic cleavage sites and polymorphic stop codons have been identified. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. [provided by RefSeq, May 2023]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRB2	ENST00000545829.1	n.364+5194G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43956 AN: 151944 Hom.: 6739 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.290 AC: 44037 AN: 152062 Hom.: 6755 Cov.: 32 AF XY: 0.291 AC XY: 21647 AN XY: 74348

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.273

Alfa AF: 0.258 Hom.: 11976

Bravo AF: 0.300

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2908835; hg19: chr12-11648418;