chr1-13596304-A-G

Variant names:

• chr1-13596304-A-G
• rs7514217
• NM_006474.5:c.68-10869A>G

Variant summary

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

The NM_006474.5(PDPN):​c.68-10869A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,992 control chromosomes in the GnomAD database, including 16,857 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 0.47 (16857 hom., cov: 32)
• Consequence: PDPN NM_006474.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 3 publications found

Genes affected

PDPN (HGNC:29602): (podoplanin) This gene encodes a type-I integral membrane glycoprotein with diverse distribution in human tissues. The physiological function of this protein may be related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor. The specific function of this protein has not been determined but it has been proposed as a marker of lung injury. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDPN	NM_006474.5	c.68-10869A>G		intron_variant	Intron 1 of 5	ENST00000621990.5	NP_006465.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDPN	ENST00000621990.5	c.68-10869A>G		intron_variant	Intron 1 of 5	1	NM_006474.5	ENSP00000478125.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70965 AN: 151876 Hom.: 16824 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.467 AC: 71050 AN: 151992 Hom.: 16857 Cov.: 32 AF XY: 0.472 AC XY: 35078 AN XY: 74300

African (AFR) AF: 0.488 AC: 20210 AN: 41424

American (AMR) AF: 0.521 AC: 7961 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1612 AN: 3472

East Asian (EAS) AF: 0.686 AC: 3553 AN: 5182

South Asian (SAS) AF: 0.549 AC: 2649 AN: 4822

European-Finnish (FIN) AF: 0.468 AC: 4934 AN: 10544

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28500 AN: 67964

Other (OTH) AF: 0.471 AC: 994 AN: 2112

Alfa AF: 0.428 Hom.: 21902

Bravo AF: 0.474

Asia WGS AF: 0.596 AC: 2071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.67
DANN	Benign	0.68
PhyloP100		-0.47
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: rs7514217; hg19: chr1-13922799; COSMIC: COSV53847208;