NM_006475.3:c.219-1999G>C

Variant names:

• chr13-37594163-C-G
• rs3923854
• NM_006475.3:c.219-1999G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006475.3(POSTN):​c.219-1999G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,784 control chromosomes in the GnomAD database, including 12,429 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 0.39 (12429 hom., cov: 33)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.219-1999G>C		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.219-1999G>C		intron_variant	Intron 2 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59863 AN: 151668 Hom.: 12427 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.395 AC: 59890 AN: 151784 Hom.: 12429 Cov.: 33 AF XY: 0.397 AC XY: 29455 AN XY: 74144

African (AFR) AF: 0.296 AC: 12256 AN: 41436

American (AMR) AF: 0.413 AC: 6300 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3464

East Asian (EAS) AF: 0.153 AC: 789 AN: 5162

South Asian (SAS) AF: 0.364 AC: 1754 AN: 4814

European-Finnish (FIN) AF: 0.503 AC: 5293 AN: 10520

Middle Eastern (MID) AF: 0.496 AC: 140 AN: 282

European-Non Finnish (NFE) AF: 0.453 AC: 30726 AN: 67838

Other (OTH) AF: 0.411 AC: 868 AN: 2110

Alfa AF: 0.409 Hom.: 1666

Bravo AF: 0.380

Asia WGS AF: 0.281 AC: 967 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.64
PhyloP100		-0.60
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: rs3923854; hg19: chr13-38168300;