13-37577065-T-G

Variant names:

• chr13-37577065-T-G
• rs9547964
• NM_006475.3:c.2008+688A>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.2008+688A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,600 control chromosomes in the GnomAD database, including 3,952 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 (3952 hom., cov: 31)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	NM_006475.3	MANE Select	c.2008+688A>C		intron	N/A	NP_006466.2
	POSTN	NM_001286665.2		c.2008+688A>C		intron	N/A	NP_001273594.1
	POSTN	NM_001330517.2		c.2008+688A>C		intron	N/A	NP_001317446.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	ENST00000379747.9	TSL:1 MANE Select	c.2008+688A>C		intron	N/A	ENSP00000369071.4
	POSTN	ENST00000379743.8	TSL:1	c.2008+688A>C		intron	N/A	ENSP00000369067.4
	POSTN	ENST00000541179.5	TSL:1	c.2008+688A>C		intron	N/A	ENSP00000437959.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32688 AN: 151480 Hom.: 3952 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.216 AC: 32702 AN: 151600 Hom.: 3952 Cov.: 31 AF XY: 0.216 AC XY: 15990 AN XY: 74058

African (AFR) AF: 0.129 AC: 5343 AN: 41334

American (AMR) AF: 0.175 AC: 2652 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3464

East Asian (EAS) AF: 0.0622 AC: 321 AN: 5158

South Asian (SAS) AF: 0.137 AC: 654 AN: 4788

European-Finnish (FIN) AF: 0.336 AC: 3522 AN: 10476

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18683 AN: 67886

Other (OTH) AF: 0.215 AC: 453 AN: 2104

Alfa AF: 0.229 Hom.: 563

Bravo AF: 0.200

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.78
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: rs9547964; hg19: chr13-38151202;