chr13-37587355-A-C

Variant names:

• chr13-37587355-A-C
• rs7336560
• NM_006475.3:c.607-427T>G

Variant summary

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

The NM_006475.3(POSTN):​c.607-427T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,918 control chromosomes in the GnomAD database, including 25,495 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 0.58 (25495 hom., cov: 31)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.607-427T>G		intron_variant	Intron 5 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.607-427T>G		intron_variant	Intron 5 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87286 AN: 151800 Hom.: 25465 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.575 AC: 87366 AN: 151918 Hom.: 25495 Cov.: 31 AF XY: 0.573 AC XY: 42551 AN XY: 74246

African (AFR) AF: 0.607 AC: 25159 AN: 41436

American (AMR) AF: 0.576 AC: 8789 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2238 AN: 3470

East Asian (EAS) AF: 0.848 AC: 4378 AN: 5160

South Asian (SAS) AF: 0.629 AC: 3030 AN: 4814

European-Finnish (FIN) AF: 0.490 AC: 5167 AN: 10554

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36894 AN: 67910

Other (OTH) AF: 0.567 AC: 1198 AN: 2114

Alfa AF: 0.573 Hom.: 4998

Bravo AF: 0.585

Asia WGS AF: 0.708 AC: 2460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.66
PhyloP100		2.3
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: rs7336560; hg19: chr13-38161492; COSMIC: COSV65714406;