rs11619443

Variant names:

• chr13-37595578-C-G
• rs11619443
• NM_006475.3:c.218+1606G>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.218+1606G>C 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 152,062 control chromosomes in the GnomAD database, including 3,710 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 (3710 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• 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.218+1606G>C		intron_variant	Intron 2 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.218+1606G>C		intron_variant	Intron 2 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30418 AN: 151944 Hom.: 3711 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.333

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: 30419 AN: 152062 Hom.: 3710 Cov.: 32 AF XY: 0.200 AC XY: 14865 AN XY: 74316

African (AFR) AF: 0.0751 AC: 3118 AN: 41516

American (AMR) AF: 0.170 AC: 2599 AN: 15274

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

East Asian (EAS) AF: 0.0618 AC: 319 AN: 5160

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

European-Finnish (FIN) AF: 0.333 AC: 3513 AN: 10534

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

European-Non Finnish (NFE) AF: 0.275 AC: 18710 AN: 67972

Other (OTH) AF: 0.204 AC: 430 AN: 2110

Alfa AF: 0.231 Hom.: 561

Bravo AF: 0.183

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	0.18
DANN	Benign	0.57
PhyloP100		-0.44
Mutation Taster		=98/2	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: rs11619443; hg19: chr13-38169715;