12-11405943-C-G

Variant names:

• chr12-11405943-C-G
• rs71455379
• ENST00000538349.5:n.300-5940G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000255790	ENST00000538349.5	n.300-5940G>C		intron_variant	Intron 3 of 4	4
ENSG00000255790	ENST00000542062.5	n.523+755G>C		intron_variant	Intron 5 of 5	4
PRB2	ENST00000545829.1	n.365-11413G>C		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.0136 AC: 564 AN: 41558

American (AMR) AF: 0.0353 AC: 539 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.00810 AC: 39 AN: 4816

European-Finnish (FIN) AF: 0.0405 AC: 429 AN: 10602

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0655 AC: 4453 AN: 68014

Other (OTH) AF: 0.0388 AC: 82 AN: 2114

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
PhyloP100		-0.37

Splicing

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

Other links and lift over

dbSNP: rs71455379; hg19: chr12-11558877;