12-11432446-G-A

Position:

• chr12-11432446-G-A

Variant summary

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

The NR_148969.1(LOC440084):​n.386-884C>T 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 0.352 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: LOC440084 NR_148969.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

Genes affected

(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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC440084	NR_148969.1	n.386-884C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000538349.5	n.219-884C>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.312

Alfa AF: 0.225 Hom.: 6295

Bravo AF: 0.384

Asia WGS AF: 0.212 AC: 738 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	0.84
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10845353; hg19: chr12-11585380;