rs2900174

Positions:

• chr12-11394598-A-G

Variant summary

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

The NM_006248.4(PRB2):​c.65-68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,569,676 control chromosomes in the GnomAD database, including 6,127 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 0.12 (2449 hom., cov: 31)
  • Exomes 𝑓: 0.045 (3678 hom.)
• Consequence: PRB2 NM_006248.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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]

PRB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRB2	NM_006248.4	c.65-68T>C		intron_variant		ENST00000389362.6	NP_006239.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRB2	ENST00000389362.6	c.65-68T>C		intron_variant		5	NM_006248.4	ENSP00000374013.4
PRB2	ENST00000545829.1	n.365-68T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18348 AN: 152058 Hom.: 2444 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0995

GnomAD4 exome AF: 0.0446 AC: 63265 AN: 1417500 Hom.: 3678 AF XY: 0.0453 AC XY: 32079 AN XY: 707676

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0224

Gnomad4 EAS exome AF: 0.0801

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.00918

Gnomad4 NFE exome AF: 0.0271

Gnomad4 OTH exome AF: 0.0555

GnomAD4 genome AF: 0.121 AC: 18381 AN: 152176 Hom.: 2449 Cov.: 31 AF XY: 0.119 AC XY: 8884 AN XY: 74416

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.00753

Gnomad4 NFE AF: 0.0266

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.0382 Hom.: 417

Bravo AF: 0.137

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.6
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2900174; hg19: chr12-11547532; COSMIC: COSV66982543; COSMIC: COSV66982543;