rs8001709

Positions:

• chr13-37577484-T-A
• chr13-37577484-T-G

Variant summary

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

The NM_006475.3(POSTN):​c.2008+269A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,124 control chromosomes in the GnomAD database, including 8,114 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 0.30 (8114 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494

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 = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POSTN	NM_006475.3	c.2008+269A>T		intron_variant		ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.2008+269A>T		intron_variant		1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46176 AN: 152004 Hom.: 8110 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.304 AC: 46190 AN: 152124 Hom.: 8114 Cov.: 32 AF XY: 0.304 AC XY: 22611 AN XY: 74352

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.0810

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.313

Alfa AF: 0.222 Hom.: 544

Bravo AF: 0.284

Asia WGS AF: 0.220 AC: 766 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	0.68
DANN	Benign	0.57

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: rs8001709; hg19: chr13-38151621;