13-37578993-T-C

Variant names:

• chr13-37578993-T-C
• rs7322993
• NM_006475.3:c.1894+26A>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.1894+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,604,724 control chromosomes in the GnomAD database, including 358,116 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 (38562 hom., cov: 29)
  • Exomes 𝑓: 0.66 (319554 hom.)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	NM_006475.3	MANE Select	c.1894+26A>G		intron	N/A	NP_006466.2	Q15063-1
	POSTN	NM_001286665.2		c.1894+26A>G		intron	N/A	NP_001273594.1	Q15063-5
	POSTN	NM_001330517.2		c.1894+26A>G		intron	N/A	NP_001317446.1	Q15063-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	ENST00000379747.9	TSL:1 MANE Select	c.1894+26A>G		intron	N/A	ENSP00000369071.4	Q15063-1
	POSTN	ENST00000379743.8	TSL:1	c.1894+26A>G		intron	N/A	ENSP00000369067.4	Q15063-5
	POSTN	ENST00000541179.5	TSL:1	c.1894+26A>G		intron	N/A	ENSP00000437959.1	Q15063-3

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107535 AN: 151762 Hom.: 38523 Cov.: 29

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.692

GnomAD2 exomes AF: 0.687 AC: 167630 AN: 243864 AF XY: 0.682

Gnomad AFR exome AF: 0.804

Gnomad AMR exome AF: 0.717

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.830

Gnomad FIN exome AF: 0.747

Gnomad NFE exome AF: 0.651

Gnomad OTH exome AF: 0.663

GnomAD4 exome AF: 0.661 AC: 960598 AN: 1452846 Hom.: 319554 Cov.: 35 AF XY: 0.660 AC XY: 477092 AN XY: 722432

African (AFR) AF: 0.803 AC: 26535 AN: 33042

American (AMR) AF: 0.715 AC: 30630 AN: 42840

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 12995 AN: 25764

East Asian (EAS) AF: 0.870 AC: 34363 AN: 39494

South Asian (SAS) AF: 0.663 AC: 56125 AN: 84668

European-Finnish (FIN) AF: 0.737 AC: 39244 AN: 53256

Middle Eastern (MID) AF: 0.681 AC: 3893 AN: 5716

European-Non Finnish (NFE) AF: 0.648 AC: 717485 AN: 1108064

Other (OTH) AF: 0.655 AC: 39328 AN: 60002

GnomAD4 genome AF: 0.709 AC: 107622 AN: 151878 Hom.: 38562 Cov.: 29 AF XY: 0.717 AC XY: 53264 AN XY: 74236

African (AFR) AF: 0.794 AC: 32896 AN: 41424

American (AMR) AF: 0.711 AC: 10838 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1767 AN: 3466

East Asian (EAS) AF: 0.837 AC: 4323 AN: 5166

South Asian (SAS) AF: 0.670 AC: 3206 AN: 4786

European-Finnish (FIN) AF: 0.753 AC: 7943 AN: 10544

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

European-Non Finnish (NFE) AF: 0.653 AC: 44323 AN: 67922

Other (OTH) AF: 0.689 AC: 1457 AN: 2114

Alfa AF: 0.663 Hom.: 7162

Bravo AF: 0.708

Asia WGS AF: 0.739 AC: 2567 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.45
PhyloP100		-1.1
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: rs7322993; hg19: chr13-38153130;