chr13-37595786-A-G

Variant names:

• chr13-37595786-A-G
• rs1977278
• NM_006475.3:c.218+1398T>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+1398T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,532 control chromosomes in the GnomAD database, including 43,771 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 0.75 (43771 hom., cov: 28)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.218+1398T>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+1398T>C		intron_variant	Intron 2 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114231 AN: 151420 Hom.: 43745 Cov.: 28

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.821

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.754 AC: 114308 AN: 151532 Hom.: 43771 Cov.: 28 AF XY: 0.746 AC XY: 55166 AN XY: 73960

African (AFR) AF: 0.728 AC: 30091 AN: 41316

American (AMR) AF: 0.729 AC: 11089 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2933 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1618 AN: 5144

South Asian (SAS) AF: 0.699 AC: 3358 AN: 4802

European-Finnish (FIN) AF: 0.756 AC: 7838 AN: 10362

Middle Eastern (MID) AF: 0.817 AC: 237 AN: 290

European-Non Finnish (NFE) AF: 0.806 AC: 54729 AN: 67922

Other (OTH) AF: 0.773 AC: 1624 AN: 2100

Alfa AF: 0.774 Hom.: 7543

Bravo AF: 0.751

Asia WGS AF: 0.557 AC: 1938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.56
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: rs1977278; hg19: chr13-38169923;