13-37585496-A-G

Variant names:

• chr13-37585496-A-G
• rs12871092
• NM_006475.3:c.896-568T>C

Variant summary

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

The NM_006475.3(POSTN):​c.896-568T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 152,276 control chromosomes in the GnomAD database, including 808 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 0.085 (808 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.896-568T>C		intron_variant	Intron 7 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.896-568T>C		intron_variant	Intron 7 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.0855 AC: 13009 AN: 152158 Hom.: 806 Cov.: 32

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0829

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.0778

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

GnomAD4 genome AF: 0.0855 AC: 13015 AN: 152276 Hom.: 808 Cov.: 32 AF XY: 0.0890 AC XY: 6629 AN XY: 74452

African (AFR) AF: 0.0372 AC: 1547 AN: 41556

American (AMR) AF: 0.121 AC: 1849 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1755 AN: 5174

South Asian (SAS) AF: 0.142 AC: 684 AN: 4828

European-Finnish (FIN) AF: 0.0829 AC: 880 AN: 10620

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0873 AC: 5940 AN: 68022

Other (OTH) AF: 0.0780 AC: 165 AN: 2116

Alfa AF: 0.0846 Hom.: 2063

Bravo AF: 0.0865

Asia WGS AF: 0.225 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.29
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12871092; hg19: chr13-38159633;