chr13-37566742-A-T

Variant names:

• chr13-37566742-A-T
• rs9547958
• NM_006475.3:c.2432-2182T>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.2432-2182T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,978 control chromosomes in the GnomAD database, including 3,708 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 0.20 (3708 hom., cov: 30)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13
• 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=-0.88).
• 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.2432-2182T>A		intron_variant	Intron 21 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.2432-2182T>A		intron_variant	Intron 21 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30399 AN: 151860 Hom.: 3709 Cov.: 30

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.200 AC: 30400 AN: 151978 Hom.: 3708 Cov.: 30 AF XY: 0.200 AC XY: 14867 AN XY: 74286

African (AFR) AF: 0.0749 AC: 3106 AN: 41476

American (AMR) AF: 0.170 AC: 2587 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3472

East Asian (EAS) AF: 0.0649 AC: 335 AN: 5158

South Asian (SAS) AF: 0.137 AC: 658 AN: 4812

European-Finnish (FIN) AF: 0.334 AC: 3523 AN: 10534

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18688 AN: 67958

Other (OTH) AF: 0.203 AC: 428 AN: 2104

Alfa AF: 0.231 Hom.: 562

Bravo AF: 0.182

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.6
DANN	Benign	0.45
PhyloP100		3.1
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: rs9547958; hg19: chr13-38140879;