7-137286354-C-T

Variant names:

• chr7-137286354-C-T
• rs3959914
• NM_002825.7:c.-1-31380G>A

Variant summary

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

The NM_002825.7(PTN):​c.-1-31380G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,952 control chromosomes in the GnomAD database, including 27,396 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 0.59 (27396 hom., cov: 32)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTN	NM_002825.7	c.-1-31380G>A		intron_variant	Intron 1 of 4	ENST00000348225.7	NP_002816.1
PTN	NM_001321387.3	c.-1-31380G>A		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.-1-31380G>A		intron_variant	Intron 1 of 4	1	NM_002825.7	ENSP00000341170.2
PTN	ENST00000699293.1	c.-1-31380G>A		intron_variant	Intron 1 of 4			ENSP00000514273.1
PTN	ENST00000393083.2	c.-1-31380G>A		intron_variant	Intron 1 of 5	5		ENSP00000376798.2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89999 AN: 151832 Hom.: 27382 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.593 AC: 90039 AN: 151952 Hom.: 27396 Cov.: 32 AF XY: 0.589 AC XY: 43740 AN XY: 74274

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.600

Alfa AF: 0.648 Hom.: 58964

Bravo AF: 0.572

Asia WGS AF: 0.520 AC: 1810 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.92
DANN	Benign	0.21

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: rs3959914; hg19: chr7-136971101;