rs4512969

chr13-37576532-A-G

Variant summary

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

The NM_006475.3(POSTN):c.2008+1221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,160 control chromosomes in the GnomAD database, including 825 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 0.088 (825 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POSTN	NM_006475.3	c.2008+1221T>C		intron_variant		ENST00000379747.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POSTN	ENST00000379747.9	c.2008+1221T>C		intron_variant		1	NM_006475.3	P3

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13419 AN: 152042 Hom.: 823 Cov.: 32

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.0890

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0882 AC: 13417 AN: 152160 Hom.: 825 Cov.: 32 AF XY: 0.0885 AC XY: 6581 AN XY: 74372

Gnomad4 AFR AF: 0.0223

Gnomad4 AMR AF: 0.0889

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.0183

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0983

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.0991

Alfa AF: 0.0983 Hom.: 124

Bravo AF: 0.0836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.42
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4512969; hg19: chr13-38150669;