chr7-137321061-G-A

Variant names:

• chr7-137321061-G-A
• rs2242045
• NM_002825.7:c.-2+22378C>T

Variant summary

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

The NM_002825.7(PTN):​c.-2+22378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,970 control chromosomes in the GnomAD database, including 13,082 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 0.39 (13082 hom., cov: 32)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• Publications: 4 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]

ENSG00000231114 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTN	NM_002825.7	c.-2+22378C>T		intron_variant	Intron 1 of 4	ENST00000348225.7	NP_002816.1
PTN	NM_001321387.3	c.-2+22378C>T		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.-2+22378C>T		intron_variant	Intron 1 of 4	1	NM_002825.7	ENSP00000341170.2
PTN	ENST00000699293.1	c.-2+22378C>T		intron_variant	Intron 1 of 4			ENSP00000514273.1
PTN	ENST00000393083.2	c.-2+22378C>T		intron_variant	Intron 1 of 5	5		ENSP00000376798.2
ENSG00000231114	ENST00000447529.1	n.266+2204G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59859 AN: 151852 Hom.: 13079 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.394 AC: 59859 AN: 151970 Hom.: 13082 Cov.: 32 AF XY: 0.392 AC XY: 29115 AN XY: 74256

African (AFR) AF: 0.224 AC: 9287 AN: 41456

American (AMR) AF: 0.324 AC: 4947 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1728 AN: 3472

East Asian (EAS) AF: 0.268 AC: 1383 AN: 5158

South Asian (SAS) AF: 0.539 AC: 2593 AN: 4812

European-Finnish (FIN) AF: 0.459 AC: 4840 AN: 10538

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33724 AN: 67962

Other (OTH) AF: 0.411 AC: 864 AN: 2102

Alfa AF: 0.452 Hom.: 49812

Bravo AF: 0.369

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		0.61
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: rs2242045; hg19: chr7-137005808;