chr13-37577484-T-A

Variant names:

• chr13-37577484-T-A
• rs8001709
• NM_006475.3:c.2008+269A>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.2008+269A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,124 control chromosomes in the GnomAD database, including 8,114 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 0.30 (8114 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 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.2008+269A>T		intron	N/A	NP_006466.2
	POSTN	NM_001286665.2		c.2008+269A>T		intron	N/A	NP_001273594.1
	POSTN	NM_001330517.2		c.2008+269A>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.2008+269A>T		intron	N/A	ENSP00000369071.4
	POSTN	ENST00000379743.8	TSL:1	c.2008+269A>T		intron	N/A	ENSP00000369067.4
	POSTN	ENST00000541179.5	TSL:1	c.2008+269A>T		intron	N/A	ENSP00000437959.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46176 AN: 152004 Hom.: 8110 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.304 AC: 46190 AN: 152124 Hom.: 8114 Cov.: 32 AF XY: 0.304 AC XY: 22611 AN XY: 74352

African (AFR) AF: 0.151 AC: 6276 AN: 41512

American (AMR) AF: 0.263 AC: 4027 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 981 AN: 3470

East Asian (EAS) AF: 0.0810 AC: 419 AN: 5176

South Asian (SAS) AF: 0.307 AC: 1479 AN: 4812

European-Finnish (FIN) AF: 0.432 AC: 4568 AN: 10578

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27167 AN: 67978

Other (OTH) AF: 0.313 AC: 659 AN: 2106

Alfa AF: 0.222 Hom.: 544

Bravo AF: 0.284

Asia WGS AF: 0.220 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.68
DANN	Benign	0.57
PhyloP100		0.49
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: rs8001709; hg19: chr13-38151621;