rs3794374

Variant names:

• chr13-37584294-C-T
• rs3794374
• NM_006475.3:c.1109-191G>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.1109-191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,994 control chromosomes in the GnomAD database, including 6,876 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 0.29 (6876 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	NM_006475.3	MANE Select	c.1109-191G>A		intron	N/A	NP_006466.2	Q15063-1
	POSTN	NM_001286665.2		c.1109-191G>A		intron	N/A	NP_001273594.1	Q15063-5
	POSTN	NM_001330517.2		c.1109-191G>A		intron	N/A	NP_001317446.1	Q15063-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	ENST00000379747.9	TSL:1 MANE Select	c.1109-191G>A		intron	N/A	ENSP00000369071.4	Q15063-1
	POSTN	ENST00000379743.8	TSL:1	c.1109-191G>A		intron	N/A	ENSP00000369067.4	Q15063-5
	POSTN	ENST00000541179.5	TSL:1	c.1109-191G>A		intron	N/A	ENSP00000437959.1	Q15063-3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44255 AN: 151878 Hom.: 6866 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.291 AC: 44284 AN: 151994 Hom.: 6876 Cov.: 32 AF XY: 0.282 AC XY: 20975 AN XY: 74274

African (AFR) AF: 0.206 AC: 8542 AN: 41486

American (AMR) AF: 0.289 AC: 4409 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1700 AN: 3466

East Asian (EAS) AF: 0.163 AC: 842 AN: 5178

South Asian (SAS) AF: 0.330 AC: 1587 AN: 4814

European-Finnish (FIN) AF: 0.246 AC: 2592 AN: 10548

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23627 AN: 67930

Other (OTH) AF: 0.312 AC: 657 AN: 2108

Alfa AF: 0.317 Hom.: 1038

Bravo AF: 0.292

Asia WGS AF: 0.260 AC: 903 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	6.0
DANN	Benign	0.45
PhyloP100		0.24
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: rs3794374; hg19: chr13-38158431; COSMIC: COSV65714395;