rs6750

Positions:

• chr13-37562695-C-G
• chr13-37562695-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006475.3(POSTN):​c.*638G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 152,098 control chromosomes in the GnomAD database, including 822 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 0.088 (822 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: POSTN NM_006475.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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]

POSTN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POSTN	NM_006475.3	c.*638G>C		3_prime_UTR_variant	23/23	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747	c.*638G>C		3_prime_UTR_variant	23/23	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13436 AN: 151976 Hom.: 820 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.250

GnomAD4 genome AF: 0.0883 AC: 13434 AN: 152094 Hom.: 822 Cov.: 32 AF XY: 0.0887 AC XY: 6595 AN XY: 74350

Gnomad4 AFR AF: 0.0223

Gnomad4 AMR AF: 0.0892

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.0187

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.0984

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0462 Hom.: 47

Bravo AF: 0.0836

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs6750; hg19: chr13-38136832;