19-35825808-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004646.4(NPHS1):​c.*706A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 152,270 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.030 ( 90 hom., cov: 32)

Consequence

NPHS1
NM_004646.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.535
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 19-35825808-T-C is Benign according to our data. Variant chr19-35825808-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 328846.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0304 (4636/152270) while in subpopulation NFE AF= 0.043 (2926/68020). AF 95% confidence interval is 0.0417. There are 90 homozygotes in gnomad4. There are 2345 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 90 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NPHS1NM_004646.4 linkuse as main transcriptc.*706A>G 3_prime_UTR_variant 29/29 ENST00000378910.10 NP_004637.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NPHS1ENST00000378910.10 linkuse as main transcriptc.*706A>G 3_prime_UTR_variant 29/291 NM_004646.4 ENSP00000368190 P2O60500-1

Frequencies

GnomAD3 genomes
AF:
0.0305
AC:
4638
AN:
152152
Hom.:
90
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00652
Gnomad AMI
AF:
0.0747
Gnomad AMR
AF:
0.0257
Gnomad ASJ
AF:
0.0467
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00808
Gnomad FIN
AF:
0.0673
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.0430
Gnomad OTH
AF:
0.0301
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0304
AC:
4636
AN:
152270
Hom.:
90
Cov.:
32
AF XY:
0.0315
AC XY:
2345
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00650
Gnomad4 AMR
AF:
0.0256
Gnomad4 ASJ
AF:
0.0467
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00808
Gnomad4 FIN
AF:
0.0673
Gnomad4 NFE
AF:
0.0430
Gnomad4 OTH
AF:
0.0298
Alfa
AF:
0.0437
Hom.:
24
Bravo
AF:
0.0258
Asia WGS
AF:
0.00433
AC:
15
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Congenital nephrotic syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
5.9
DANN
Benign
0.75

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs80296922; hg19: chr19-36316710; API