rs9547965

Variant names:

• chr13-37579751-G-A
• rs9547965
• NM_006475.3:c.1660+110C>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.1660+110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,225,784 control chromosomes in the GnomAD database, including 40,630 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 0.22 (3959 hom., cov: 33)
  • Exomes 𝑓: 0.26 (36671 hom.)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.1660+110C>T		intron_variant	Intron 12 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.1660+110C>T		intron_variant	Intron 12 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32743 AN: 151954 Hom.: 3959 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0618

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.256 AC: 274513 AN: 1073712 Hom.: 36671 AF XY: 0.253 AC XY: 135441 AN XY: 535398

African (AFR) AF: 0.128 AC: 3036 AN: 23798

American (AMR) AF: 0.178 AC: 4067 AN: 22872

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 3653 AN: 17918

East Asian (EAS) AF: 0.102 AC: 3569 AN: 34980

South Asian (SAS) AF: 0.154 AC: 9281 AN: 60194

European-Finnish (FIN) AF: 0.329 AC: 13646 AN: 41520

Middle Eastern (MID) AF: 0.204 AC: 835 AN: 4092

European-Non Finnish (NFE) AF: 0.275 AC: 226001 AN: 821934

Other (OTH) AF: 0.225 AC: 10425 AN: 46404

GnomAD4 genome AF: 0.215 AC: 32757 AN: 152072 Hom.: 3959 Cov.: 33 AF XY: 0.216 AC XY: 16018 AN XY: 74326

African (AFR) AF: 0.129 AC: 5357 AN: 41510

American (AMR) AF: 0.174 AC: 2665 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3470

East Asian (EAS) AF: 0.0621 AC: 321 AN: 5166

South Asian (SAS) AF: 0.136 AC: 657 AN: 4822

European-Finnish (FIN) AF: 0.334 AC: 3527 AN: 10546

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18700 AN: 67968

Other (OTH) AF: 0.216 AC: 455 AN: 2110

Alfa AF: 0.236 Hom.: 583

Bravo AF: 0.200

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.75
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9547965; hg19: chr13-38153888; COSMIC: COSV65712983;