rs1977278

chr13-37595786-A-Gchr13-37595786-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006475.3(POSTN):c.218+1398T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,532 control chromosomes in the GnomAD database, including 43,771 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 0.75 (43771 hom., cov: 28)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POSTN	NM_006475.3	c.218+1398T>C		intron_variant		ENST00000379747.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POSTN	ENST00000379747.9	c.218+1398T>C		intron_variant		1	NM_006475.3	P3

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114231 AN: 151420 Hom.: 43745 Cov.: 28

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.821

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.754 AC: 114308 AN: 151532 Hom.: 43771 Cov.: 28 AF XY: 0.746 AC XY: 55166 AN XY: 73960

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.773

Alfa AF: 0.775 Hom.: 7332

Bravo AF: 0.751

Asia WGS AF: 0.557 AC: 1938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs1977278; hg19: chr13-38169923;