rs6750

Variant names:

• chr13-37562695-C-G
• rs6750
• NM_006475.3:c.*638G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-37562695-C-G
• chr13-37562695-C-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.*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
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 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.*638G>C		3_prime_UTR	Exon 23 of 23	NP_006466.2
	POSTN	NM_001286665.2		c.*638G>C		3_prime_UTR	Exon 22 of 22	NP_001273594.1
	POSTN	NM_001330517.2		c.*638G>C		3_prime_UTR	Exon 22 of 22	NP_001317446.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	ENST00000379747.9	TSL:1 MANE Select	c.*638G>C		3_prime_UTR	Exon 23 of 23	ENSP00000369071.4
	POSTN	ENST00000379743.8	TSL:1	c.*638G>C		3_prime_UTR	Exon 22 of 22	ENSP00000369067.4
	POSTN	ENST00000541179.5	TSL:1	c.*638G>C		3_prime_UTR	Exon 21 of 21	ENSP00000437959.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0223 AC: 925 AN: 41506

American (AMR) AF: 0.0892 AC: 1362 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3472

East Asian (EAS) AF: 0.0187 AC: 97 AN: 5180

South Asian (SAS) AF: 0.171 AC: 825 AN: 4822

European-Finnish (FIN) AF: 0.0984 AC: 1039 AN: 10562

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8457 AN: 67966

Other (OTH) AF: 0.100 AC: 211 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.70
PhyloP100		0.14
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: rs6750; hg19: chr13-38136832;