NM_006475.3:c.606+396C>T

Variant names:

• chr13-37587426-G-A
• rs9576309
• NM_006475.3:c.606+396C>T

Variant summary

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

The NM_006475.3(POSTN):​c.606+396C>T 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 152,032 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: -2.02
• 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=-0.93).
• 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 rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.606+396C>T		intron_variant	Intron 5 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.606+396C>T		intron_variant	Intron 5 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44249 AN: 151912 Hom.: 6866 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.291 AC: 44278 AN: 152032 Hom.: 6876 Cov.: 32 AF XY: 0.282 AC XY: 20991 AN XY: 74320

African (AFR) AF: 0.206 AC: 8540 AN: 41472

American (AMR) AF: 0.289 AC: 4417 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3466

East Asian (EAS) AF: 0.163 AC: 843 AN: 5170

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4822

European-Finnish (FIN) AF: 0.247 AC: 2609 AN: 10568

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23596 AN: 67950

Other (OTH) AF: 0.310 AC: 655 AN: 2114

Alfa AF: 0.315 Hom.: 1385

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	-0.93
CADD	Benign	0.019
DANN	Benign	0.52
PhyloP100		-2.0
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: rs9576309; hg19: chr13-38161563;