NM_006475.3:c.2432-33G>A

Variant names:

• chr13-37564593-C-T
• rs4390468
• NM_006475.3:c.2432-33G>A

Variant summary

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

The NM_006475.3(POSTN):​c.2432-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,435,422 control chromosomes in the GnomAD database, including 316,504 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 0.71 (38448 hom., cov: 30)
  • Exomes 𝑓: 0.66 (278056 hom.)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 13 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=-0.81).
• 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 rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.2432-33G>A		intron_variant	Intron 21 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.2432-33G>A		intron_variant	Intron 21 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107299 AN: 151502 Hom.: 38411 Cov.: 30

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.691

GnomAD2 exomes AF: 0.686 AC: 167798 AN: 244512 AF XY: 0.681

Gnomad AFR exome AF: 0.802

Gnomad AMR exome AF: 0.715

Gnomad ASJ exome AF: 0.501

Gnomad EAS exome AF: 0.830

Gnomad FIN exome AF: 0.746

Gnomad NFE exome AF: 0.651

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.656 AC: 842228 AN: 1283800 Hom.: 278056 Cov.: 18 AF XY: 0.656 AC XY: 424645 AN XY: 647326

African (AFR) AF: 0.797 AC: 23458 AN: 29450

American (AMR) AF: 0.713 AC: 30701 AN: 43048

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 12515 AN: 24920

East Asian (EAS) AF: 0.870 AC: 33514 AN: 38500

South Asian (SAS) AF: 0.661 AC: 53365 AN: 80774

European-Finnish (FIN) AF: 0.737 AC: 39015 AN: 52966

Middle Eastern (MID) AF: 0.679 AC: 3662 AN: 5396

European-Non Finnish (NFE) AF: 0.640 AC: 610597 AN: 954310

Other (OTH) AF: 0.650 AC: 35401 AN: 54436

GnomAD4 genome AF: 0.708 AC: 107386 AN: 151622 Hom.: 38448 Cov.: 30 AF XY: 0.717 AC XY: 53112 AN XY: 74068

African (AFR) AF: 0.792 AC: 32808 AN: 41410

American (AMR) AF: 0.710 AC: 10827 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1770 AN: 3466

East Asian (EAS) AF: 0.837 AC: 4299 AN: 5136

South Asian (SAS) AF: 0.671 AC: 3235 AN: 4818

European-Finnish (FIN) AF: 0.755 AC: 7954 AN: 10534

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44172 AN: 67702

Other (OTH) AF: 0.689 AC: 1448 AN: 2102

Alfa AF: 0.665 Hom.: 133132

Bravo AF: 0.707

Asia WGS AF: 0.739 AC: 2565 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.76
PhyloP100		0.092
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: rs4390468; hg19: chr13-38138730; COSMIC: COSV65711911; COSMIC: COSV65711911;