13-37590308-G-A

Variant names:

• chr13-37590308-G-A
• rs1006416
• NM_006475.3:c.441+64C>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.441+64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,282,232 control chromosomes in the GnomAD database, including 362,687 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 0.79 (47355 hom., cov: 32)
  • Exomes 𝑓: 0.75 (315332 hom.)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 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.441+64C>T		intron	N/A	NP_006466.2
	POSTN	NM_001286665.2		c.441+64C>T		intron	N/A	NP_001273594.1
	POSTN	NM_001330517.2		c.441+64C>T		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.441+64C>T		intron	N/A	ENSP00000369071.4
	POSTN	ENST00000379743.8	TSL:1	c.441+64C>T		intron	N/A	ENSP00000369067.4
	POSTN	ENST00000541179.5	TSL:1	c.441+64C>T		intron	N/A	ENSP00000437959.1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119367 AN: 151996 Hom.: 47308 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.792

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.745 AC: 842056 AN: 1130118 Hom.: 315332 AF XY: 0.747 AC XY: 418754 AN XY: 560626

African (AFR) AF: 0.875 AC: 21814 AN: 24932

American (AMR) AF: 0.818 AC: 19238 AN: 23510

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 15922 AN: 20016

East Asian (EAS) AF: 0.896 AC: 30287 AN: 33814

South Asian (SAS) AF: 0.845 AC: 48340 AN: 57186

European-Finnish (FIN) AF: 0.671 AC: 29982 AN: 44664

Middle Eastern (MID) AF: 0.800 AC: 3650 AN: 4564

European-Non Finnish (NFE) AF: 0.728 AC: 635256 AN: 873136

Other (OTH) AF: 0.778 AC: 37567 AN: 48296

GnomAD4 genome AF: 0.785 AC: 119473 AN: 152114 Hom.: 47355 Cov.: 32 AF XY: 0.785 AC XY: 58389 AN XY: 74346

African (AFR) AF: 0.873 AC: 36254 AN: 41514

American (AMR) AF: 0.826 AC: 12622 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2735 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4854 AN: 5182

South Asian (SAS) AF: 0.864 AC: 4169 AN: 4828

European-Finnish (FIN) AF: 0.667 AC: 7035 AN: 10540

Middle Eastern (MID) AF: 0.790 AC: 229 AN: 290

European-Non Finnish (NFE) AF: 0.725 AC: 49282 AN: 67988

Other (OTH) AF: 0.787 AC: 1663 AN: 2114

Alfa AF: 0.765 Hom.: 5788

Bravo AF: 0.801

Asia WGS AF: 0.853 AC: 2959 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.43
PhyloP100		-0.77
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: rs1006416; hg19: chr13-38164445;