ENST00000538349.5:n.219-884C>T

Variant names:

• chr12-11432446-G-A
• rs10845353
• ENST00000538349.5:n.219-884C>T

Variant summary

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

The ENST00000538349.5(ENSG00000255790):​n.219-884C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,118 control chromosomes in the GnomAD database, including 13,554 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 0.35 (13554 hom., cov: 32)
• Consequence: ENSG00000255790 ENST00000538349.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 3 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000538349.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC440084	NR_148969.1		n.386-884C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000255790	ENST00000538349.5	TSL:4	n.219-884C>T		intron	N/A
	ENSG00000255790	ENST00000539178.5	TSL:5	n.52-884C>T		intron	N/A
	ENSG00000255790	ENST00000540635.1	TSL:3	n.340-884C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53412 AN: 152000 Hom.: 13499 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.352 AC: 53525 AN: 152118 Hom.: 13554 Cov.: 32 AF XY: 0.348 AC XY: 25864 AN XY: 74360

African (AFR) AF: 0.714 AC: 29600 AN: 41480

American (AMR) AF: 0.346 AC: 5282 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3470

East Asian (EAS) AF: 0.171 AC: 887 AN: 5184

South Asian (SAS) AF: 0.261 AC: 1256 AN: 4812

European-Finnish (FIN) AF: 0.176 AC: 1858 AN: 10574

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12967 AN: 68000

Other (OTH) AF: 0.312 AC: 658 AN: 2110

Alfa AF: 0.274 Hom.: 15256

Bravo AF: 0.384

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.59
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs10845353; hg19: chr12-11585380;