chr7-137295427-A-G

Variant names:

• chr7-137295427-A-G
• rs919581
• NM_002825.7:c.-1-40453T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002825.7(PTN):​c.-1-40453T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,108 control chromosomes in the GnomAD database, including 1,646 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 0.13 (1646 hom., cov: 32)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 8 publications found

Genes affected

PTN (HGNC:9630): (pleiotrophin) The protein encoded by this gene is a secreted heparin-binding growth factor. The protein has significant roles in cell growth and survival, cell migration, angiogenesis and tumorigenesis. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTN	NM_002825.7	c.-1-40453T>C		intron_variant	Intron 1 of 4	ENST00000348225.7	NP_002816.1
PTN	NM_001321387.3	c.-1-40453T>C		intron_variant	Intron 1 of 4		NP_001308316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTN	ENST00000348225.7	c.-1-40453T>C		intron_variant	Intron 1 of 4	1	NM_002825.7	ENSP00000341170.2
PTN	ENST00000699293.1	c.-1-40453T>C		intron_variant	Intron 1 of 4			ENSP00000514273.1
PTN	ENST00000393083.2	c.-1-40453T>C		intron_variant	Intron 1 of 5	5		ENSP00000376798.2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20090 AN: 151990 Hom.: 1644 Cov.: 32

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.132 AC: 20088 AN: 152108 Hom.: 1646 Cov.: 32 AF XY: 0.132 AC XY: 9846 AN XY: 74346

African (AFR) AF: 0.0384 AC: 1594 AN: 41542

American (AMR) AF: 0.139 AC: 2126 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3472

East Asian (EAS) AF: 0.176 AC: 904 AN: 5122

South Asian (SAS) AF: 0.206 AC: 996 AN: 4826

European-Finnish (FIN) AF: 0.133 AC: 1410 AN: 10584

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12087 AN: 67970

Other (OTH) AF: 0.135 AC: 285 AN: 2112

Alfa AF: 0.166 Hom.: 3582

Bravo AF: 0.128

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.31
PhyloP100		0.079
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: rs919581; hg19: chr7-136980174; COSMIC: COSV61970403;