12-11405943-C-G

Position:

• chr12-11405943-C-G

Variant summary

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

The ENST00000538349.5(ENSG00000255790):​n.300-5940G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 152,248 control chromosomes in the GnomAD database, including 200 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 0.042 (200 hom., cov: 32)
• Consequence: ENSG00000255790 ENST00000538349.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

Genes affected

ENSG00000255790 (HGNC:):

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0639 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
ENSG00000255790	ENST00000538349.5	n.300-5940G>C		intron_variant		4
ENSG00000255790	ENST00000542062.5	n.523+755G>C		intron_variant		4
PRB2	ENST00000545829.1	n.365-11413G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0418 AC: 6366 AN: 152130 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00809

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0418 AC: 6366 AN: 152248 Hom.: 200 Cov.: 32 AF XY: 0.0400 AC XY: 2974 AN XY: 74436

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00810

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.0655

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0115 Hom.: 3

Bravo AF: 0.0408

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71455379; hg19: chr12-11558877;