rs9547951

Positions:

• chr13-37562545-A-C
• chr13-37562545-A-G
• chr13-37562545-A-T

Variant summary

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

The 13-37562545-A-C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,006 control chromosomes in the GnomAD database, including 35,144 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 0.68 (35144 hom., cov: 31)
  • Exomes 𝑓: 0.67 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: POSTN NM_006475.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

Genes affected

POSTN (HGNC:16953): (periostin) This gene encodes a secreted extracellular matrix protein that functions in tissue development and regeneration, including wound healing, and ventricular remodeling following myocardial infarction. The encoded protein binds to integrins to support adhesion and migration of epithelial cells. This protein plays a role in cancer stem cell maintenance and metastasis. Mice lacking this gene exhibit cardiac valve disease, and skeletal and dental defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

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 (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POSTN	NM_006475.3			downstream_gene_variant		ENST00000379747.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POSTN	ENST00000379747.9			downstream_gene_variant		1	NM_006475.3	P3

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102969 AN: 151888 Hom.: 35114 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.667

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.673 AC: 35 AN: 52 Hom.: 11 Cov.: 0 AF XY: 0.639 AC XY: 23 AN XY: 36

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.678 AC: 103044 AN: 152006 Hom.: 35144 Cov.: 31 AF XY: 0.687 AC XY: 51058 AN XY: 74286

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.664

Alfa AF: 0.573 Hom.: 1792

Bravo AF: 0.672

Asia WGS AF: 0.733 AC: 2551 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	2.9
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9547951; hg19: chr13-38136682;