chr1-5863916-G-A
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS1
The NM_015102.5(NPHP4):c.4114C>T(p.Leu1372Leu) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015102.5 synonymous
Scores
Clinical Significance
Conservation
Publications
- nephronophthisis 4Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
- Senior-Loken syndrome 4Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- nephronophthisis 1Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Senior-Loken syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPHP4 | NM_015102.5 | c.4114C>T | p.Leu1372Leu | synonymous_variant | Exon 29 of 30 | ENST00000378156.9 | NP_055917.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPHP4 | ENST00000378156.9 | c.4114C>T | p.Leu1372Leu | synonymous_variant | Exon 29 of 30 | 1 | NM_015102.5 | ENSP00000367398.4 | ||
NPHP4 | ENST00000378169.7 | n.*3015C>T | non_coding_transcript_exon_variant | Exon 26 of 27 | 1 | ENSP00000367411.3 | ||||
NPHP4 | ENST00000489180.6 | n.*1925C>T | non_coding_transcript_exon_variant | Exon 32 of 33 | 2 | ENSP00000423747.1 | ||||
NPHP4 | ENST00000378169.7 | n.*3015C>T | 3_prime_UTR_variant | Exon 26 of 27 | 1 | ENSP00000367411.3 | ||||
NPHP4 | ENST00000489180.6 | n.*1925C>T | 3_prime_UTR_variant | Exon 32 of 33 | 2 | ENSP00000423747.1 |
Frequencies
GnomAD3 genomes AF: 0.000585 AC: 89AN: 152180Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.000385 AC: 96AN: 249064 AF XY: 0.000274 show subpopulations
GnomAD4 exome AF: 0.000173 AC: 253AN: 1461668Hom.: 0 Cov.: 32 AF XY: 0.000155 AC XY: 113AN XY: 727122 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000584 AC: 89AN: 152298Hom.: 0 Cov.: 33 AF XY: 0.000457 AC XY: 34AN XY: 74472 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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Senior-Loken syndrome 4 Uncertain:1
This 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Nephronophthisis 4 Uncertain:1
This 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Benign:1
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Nephronophthisis Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at