rs4731799

Positions:

• chr7-131513416-G-A

Variant summary

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

The NM_001018111.3(PODXL):​c.101-1983C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,098 control chromosomes in the GnomAD database, including 11,719 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 0.36 (11719 hom., cov: 32)
• Consequence: PODXL NM_001018111.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

Genes affected

PODXL (HGNC:9171): (podocalyxin like) This gene encodes a member of the sialomucin protein family. The encoded protein was originally identified as an important component of glomerular podocytes. Podocytes are highly differentiated epithelial cells with interdigitating foot processes covering the outer aspect of the glomerular basement membrane. Other biological activities of the encoded protein include: binding in a membrane protein complex with Na+/H+ exchanger regulatory factor to intracellular cytoskeletal elements, playing a role in hematopoetic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin. [provided by RefSeq, Jul 2008]

PODXL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PODXL	NM_001018111.3	c.101-1983C>T		intron_variant		ENST00000378555.8	NP_001018121.1
PODXL	NM_005397.4	c.101-1983C>T		intron_variant			NP_005388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PODXL	ENST00000378555.8	c.101-1983C>T		intron_variant		1	NM_001018111.3	ENSP00000367817.3
PODXL	ENST00000322985.9	c.101-1983C>T		intron_variant		1		ENSP00000319782.9
PODXL	ENST00000446198.5	n.101-1983C>T		intron_variant		2		ENSP00000390152.1
PODXL	ENST00000465001.1	n.292-1983C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54038 AN: 151978 Hom.: 11702 Cov.: 32

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.356 AC: 54071 AN: 152098 Hom.: 11719 Cov.: 32 AF XY: 0.359 AC XY: 26711 AN XY: 74344

Gnomad4 AFR AF: 0.0952

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.371

Alfa AF: 0.443 Hom.: 24897

Bravo AF: 0.337

Asia WGS AF: 0.510 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.65

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: rs4731799; hg19: chr7-131198175; COSMIC: COSV59869734; COSMIC: COSV59869734;