chr13-37585119-A-G

Variant names:

• chr13-37585119-A-G
• rs17256386
• NM_006475.3:c.896-191T>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.896-191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,182 control chromosomes in the GnomAD database, including 6,886 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 0.29 (6886 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.896-191T>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.896-191T>C		intron_variant	Intron 7 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44293 AN: 152064 Hom.: 6876 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.291 AC: 44322 AN: 152182 Hom.: 6886 Cov.: 32 AF XY: 0.282 AC XY: 21005 AN XY: 74402

African (AFR) AF: 0.206 AC: 8550 AN: 41532

American (AMR) AF: 0.290 AC: 4426 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1702 AN: 3472

East Asian (EAS) AF: 0.163 AC: 842 AN: 5180

South Asian (SAS) AF: 0.328 AC: 1584 AN: 4822

European-Finnish (FIN) AF: 0.245 AC: 2599 AN: 10602

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23631 AN: 67976

Other (OTH) AF: 0.310 AC: 655 AN: 2112

Alfa AF: 0.315 Hom.: 1383

Bravo AF: 0.292

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.40
PhyloP100		0.65
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: rs17256386; hg19: chr13-38159256; COSMIC: COSV65714398;