chr13-37598759-G-C

Variant names:

• chr13-37598759-G-C
• rs3829365
• NM_006475.3:c.-33C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006475.3(POSTN):​c.-33C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0953 in 1,608,544 control chromosomes in the GnomAD database, including 9,485 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 0.085 (804 hom., cov: 32)
  • Exomes 𝑓: 0.096 (8681 hom.)
• Consequence: POSTN NM_006475.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72
• Publications: 23 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]

ENSG00000297050 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.-33C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 23	ENST00000379747.9	NP_006466.2
POSTN	NM_006475.3	c.-33C>G		5_prime_UTR_variant	Exon 1 of 23	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.-33C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 23	1	NM_006475.3	ENSP00000369071.4
POSTN	ENST00000379747.9	c.-33C>G		5_prime_UTR_variant	Exon 1 of 23	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.0851 AC: 12940 AN: 152012 Hom.: 803 Cov.: 32

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.0766

GnomAD2 exomes AF: 0.114 AC: 28532 AN: 250116 AF XY: 0.113

Gnomad AFR exome AF: 0.0361

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.0343

Gnomad EAS exome AF: 0.350

Gnomad FIN exome AF: 0.0830

Gnomad NFE exome AF: 0.0847

Gnomad OTH exome AF: 0.0937

GnomAD4 exome AF: 0.0964 AC: 140365 AN: 1456414 Hom.: 8681 Cov.: 31 AF XY: 0.0974 AC XY: 70561 AN XY: 724524

African (AFR) AF: 0.0331 AC: 1103 AN: 33362

American (AMR) AF: 0.140 AC: 6227 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 882 AN: 25918

East Asian (EAS) AF: 0.330 AC: 13069 AN: 39570

South Asian (SAS) AF: 0.141 AC: 12052 AN: 85670

European-Finnish (FIN) AF: 0.0874 AC: 4635 AN: 53050

Middle Eastern (MID) AF: 0.0469 AC: 268 AN: 5720

European-Non Finnish (NFE) AF: 0.0868 AC: 96167 AN: 1108404

Other (OTH) AF: 0.0992 AC: 5962 AN: 60116

GnomAD4 genome AF: 0.0851 AC: 12940 AN: 152130 Hom.: 804 Cov.: 32 AF XY: 0.0884 AC XY: 6574 AN XY: 74358

African (AFR) AF: 0.0364 AC: 1512 AN: 41540

American (AMR) AF: 0.120 AC: 1837 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3466

East Asian (EAS) AF: 0.339 AC: 1744 AN: 5142

South Asian (SAS) AF: 0.141 AC: 681 AN: 4826

European-Finnish (FIN) AF: 0.0826 AC: 875 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0873 AC: 5935 AN: 67992

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

Alfa AF: 0.0788 Hom.: 113

Bravo AF: 0.0863

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Benign	0.94
PhyloP100		5.7
PromoterAI		-0.0023	Neutral
Mutation Taster		=300/0	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: rs3829365; hg19: chr13-38172896; COSMIC: COSV65712334; COSMIC: COSV65712334;