rs9603226

Variant names:

• chr13-37569449-G-A
• rs9603226
• NM_006475.3:c.2348-66C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-37569449-G-A
• chr13-37569449-G-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.2348-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,222,192 control chromosomes in the GnomAD database, including 10,436 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 0.14 (1661 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8775 hom.)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.2348-66C>T		intron_variant	Intron 20 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.2348-66C>T		intron_variant	Intron 20 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21337 AN: 151824 Hom.: 1659 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.118 AC: 126657 AN: 1070250 Hom.: 8775 Cov.: 15 AF XY: 0.119 AC XY: 65426 AN XY: 549622

African (AFR) AF: 0.172 AC: 4319 AN: 25058

American (AMR) AF: 0.137 AC: 5785 AN: 42190

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 2688 AN: 23124

East Asian (EAS) AF: 0.335 AC: 12607 AN: 37648

South Asian (SAS) AF: 0.132 AC: 10074 AN: 76514

European-Finnish (FIN) AF: 0.153 AC: 7977 AN: 52300

Middle Eastern (MID) AF: 0.119 AC: 590 AN: 4952

European-Non Finnish (NFE) AF: 0.101 AC: 76626 AN: 761056

Other (OTH) AF: 0.126 AC: 5991 AN: 47408

GnomAD4 genome AF: 0.141 AC: 21349 AN: 151942 Hom.: 1661 Cov.: 32 AF XY: 0.145 AC XY: 10803 AN XY: 74292

African (AFR) AF: 0.165 AC: 6842 AN: 41508

American (AMR) AF: 0.144 AC: 2198 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1770 AN: 5156

South Asian (SAS) AF: 0.158 AC: 761 AN: 4828

European-Finnish (FIN) AF: 0.161 AC: 1705 AN: 10580

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7275 AN: 67822

Other (OTH) AF: 0.135 AC: 284 AN: 2106

Alfa AF: 0.116 Hom.: 3237

Bravo AF: 0.140

Asia WGS AF: 0.211 AC: 732 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.69
PhyloP100		-0.46
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: rs9603226; hg19: chr13-38143586; COSMIC: COSV65713191; COSMIC: COSV65713191;