chr13-37583283-A-T

Variant names:

• chr13-37583283-A-T
• rs17056105
• NM_006475.3:c.1243+686T>A

Variant summary

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

The NM_006475.3(POSTN):​c.1243+686T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 152,062 control chromosomes in the GnomAD database, including 796 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 0.091 (796 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472
• Publications: 1 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.1243+686T>A		intron_variant	Intron 9 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.1243+686T>A		intron_variant	Intron 9 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13872 AN: 151944 Hom.: 795 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0716

Gnomad EAS AF: 0.0708

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0955

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

GnomAD4 genome AF: 0.0913 AC: 13882 AN: 152062 Hom.: 796 Cov.: 32 AF XY: 0.0925 AC XY: 6880 AN XY: 74346

African (AFR) AF: 0.140 AC: 5798 AN: 41466

American (AMR) AF: 0.146 AC: 2229 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 248 AN: 3466

East Asian (EAS) AF: 0.0710 AC: 367 AN: 5172

South Asian (SAS) AF: 0.0621 AC: 299 AN: 4816

European-Finnish (FIN) AF: 0.0765 AC: 808 AN: 10564

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.0568 AC: 3863 AN: 68006

Other (OTH) AF: 0.0945 AC: 199 AN: 2106

Alfa AF: 0.0745 Hom.: 60

Bravo AF: 0.0975

Asia WGS AF: 0.0630 AC: 220 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.8
DANN	Benign	0.62
PhyloP100		0.47
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: rs17056105; hg19: chr13-38157420;