NM_006475.3:c.219-752C>G

Variant names:

• chr13-37592916-G-C
• rs7338244
• NM_006475.3:c.219-752C>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.219-752C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,930 control chromosomes in the GnomAD database, including 4,679 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 0.23 (4679 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.219-752C>G		intron_variant	Intron 2 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.219-752C>G		intron_variant	Intron 2 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35025 AN: 151812 Hom.: 4676 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.231 AC: 35051 AN: 151930 Hom.: 4679 Cov.: 32 AF XY: 0.239 AC XY: 17761 AN XY: 74242

African (AFR) AF: 0.220 AC: 9124 AN: 41468

American (AMR) AF: 0.267 AC: 4065 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 484 AN: 3468

East Asian (EAS) AF: 0.686 AC: 3551 AN: 5178

South Asian (SAS) AF: 0.301 AC: 1448 AN: 4816

European-Finnish (FIN) AF: 0.245 AC: 2568 AN: 10502

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.194 AC: 13185 AN: 67946

Other (OTH) AF: 0.216 AC: 454 AN: 2104

Alfa AF: 0.217 Hom.: 450

Bravo AF: 0.232

Asia WGS AF: 0.438 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.32
PhyloP100		0.19
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: rs7338244; hg19: chr13-38167053;