19-35852304-GTCTCTCTCTCTC-GTCTCTCTCTC

Position:

• chr19-35852304-GTCTCTCTCTCTC-GTCTCTCTCTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004646.4(NPHS1):​c.-469_-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 0.0869 in 144,406 control chromosomes in the GnomAD database, including 967 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (967 hom., cov: 29)
• Consequence: NPHS1 NM_004646.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.11

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 19-35852304-GTC-G is Benign according to our data. Variant chr19-35852304-GTC-G is described in ClinVar as [Benign]. Clinvar id is 1260809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHS1	NM_004646.4	c.-469_-468del		5_prime_UTR_variant	1/29	ENST00000378910.10	NP_004637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHS1	ENST00000378910.10	c.-469_-468del		5_prime_UTR_variant	1/29	1	NM_004646.4	ENSP00000368190	P2
NPHS1	ENST00000591817.1	n.560-634_560-633del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 12486 AN: 144336 Hom.: 948 Cov.: 29

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0379

Gnomad AMR AF: 0.0473

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.00663

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0359

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0729

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

GnomAD4 genome AF: 0.0869 AC: 12542 AN: 144406 Hom.: 967 Cov.: 29 AF XY: 0.0857 AC XY: 6012 AN XY: 70180

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.00665

Gnomad4 SAS AF: 0.0392

Gnomad4 FIN AF: 0.0498

Gnomad4 NFE AF: 0.0351

Gnomad4 OTH AF: 0.0724

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Finnish congenital nephrotic syndrome Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Aug 30, 2019

- -

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;