rs139954720

Positions:

• chr19-35852304-GTCTCTCTCTCTC-G
• chr19-35852304-GTCTCTCTCTCTC-GTC
• chr19-35852304-GTCTCTCTCTCTC-GTCTC
• chr19-35852304-GTCTCTCTCTCTC-GTCTCTC
• chr19-35852304-GTCTCTCTCTCTC-GTCTCTCTC
• chr19-35852304-GTCTCTCTCTCTC-GTCTCTCTCTC
• chr19-35852304-GTCTCTCTCTCTC-GTCTCTCTCTCTCTC
• chr19-35852304-GTCTCTCTCTCTC-GTCTCTCTCTCTCTCTC
• chr19-35852304-GTCTCTCTCTCTC-GTCTCTCTCTCTCTCTCTC
• chr19-35852304-GTCTCTCTCTCTC-GTCTCTCTCTCTCTCTCTCTCTC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004646.4(NPHS1):​c.-479_-468del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 145,092 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000069 (0 hom., cov: 29)
• Consequence: NPHS1 NM_004646.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

Genes affected

NPHS1 (HGNC:7908): (NPHS1 adhesion molecule, nephrin) This gene encodes a member of the immunoglobulin family of cell adhesion molecules that functions in the glomerular filtration barrier in the kidney. The gene is primarily expressed in renal tissues, and the protein is a type-1 transmembrane protein found at the slit diaphragm of glomerular podocytes. The slit diaphragm is thought to function as an ultrafilter to exclude albumin and other plasma macromolecules in the formation of urine. Mutations in this gene result in Finnish-type congenital nephrosis 1, characterized by severe proteinuria and loss of the slit diaphragm and foot processes.[provided by RefSeq, Oct 2009]

KIRREL2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPHS1	NM_004646.4	c.-479_-468del		5_prime_UTR_variant	1/29	ENST00000378910.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPHS1	ENST00000378910.10	c.-479_-468del		5_prime_UTR_variant	1/29	1	NM_004646.4	P2
NPHS1	ENST00000591817.1	n.560-644_560-633del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00000689 AC: 1 AN: 145092 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000689 AC: 1 AN: 145092 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 70486

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000153

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139954720; hg19: chr19-36343206;