13-37598099-A-G

Variant names:

• chr13-37598099-A-G
• rs4432141
• NM_006475.3:c.119+509T>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.119+509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,148 control chromosomes in the GnomAD database, including 3,721 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 0.20 (3721 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 2 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]

ENSG00000297050 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.119+509T>C		intron_variant	Intron 1 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.119+509T>C		intron_variant	Intron 1 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30551 AN: 152030 Hom.: 3722 Cov.: 32

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.201 AC: 30553 AN: 152148 Hom.: 3721 Cov.: 32 AF XY: 0.201 AC XY: 14927 AN XY: 74384

African (AFR) AF: 0.0779 AC: 3238 AN: 41550

American (AMR) AF: 0.170 AC: 2595 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3472

East Asian (EAS) AF: 0.0636 AC: 330 AN: 5186

South Asian (SAS) AF: 0.136 AC: 657 AN: 4830

European-Finnish (FIN) AF: 0.334 AC: 3524 AN: 10548

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18704 AN: 67974

Other (OTH) AF: 0.203 AC: 430 AN: 2116

Alfa AF: 0.219 Hom.: 545

Bravo AF: 0.183

Asia WGS AF: 0.142 AC: 493 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.61
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: rs4432141; hg19: chr13-38172236;