rs3794374

Positions:

• chr13-37584294-C-T

Variant summary

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

The NM_006475.3(POSTN):​c.1109-191G>A 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 151,994 control chromosomes in the GnomAD database, including 6,876 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 (6876 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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=-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/exons	MANE	Protein	UniProt
POSTN	NM_006475.3	c.1109-191G>A		intron_variant		ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.1109-191G>A		intron_variant		1	NM_006475.3	ENSP00000369071	P3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44255 AN: 151878 Hom.: 6866 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.291 AC: 44284 AN: 151994 Hom.: 6876 Cov.: 32 AF XY: 0.282 AC XY: 20975 AN XY: 74274

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.312

Alfa AF: 0.322 Hom.: 1024

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	6.0
DANN	Benign	0.45

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: rs3794374; hg19: chr13-38158431; COSMIC: COSV65714395;