chr1-5873324-C-G
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_015102.5(NPHP4):c.3243G>C(p.Gly1081Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,613,720 control chromosomes in the GnomAD database, including 548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
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
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPHP4 | NM_015102.5 | c.3243G>C | p.Gly1081Gly | synonymous_variant | Exon 23 of 30 | ENST00000378156.9 | NP_055917.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPHP4 | ENST00000378156.9 | c.3243G>C | p.Gly1081Gly | synonymous_variant | Exon 23 of 30 | 1 | NM_015102.5 | ENSP00000367398.4 | ||
NPHP4 | ENST00000378169.7 | n.*2144G>C | non_coding_transcript_exon_variant | Exon 20 of 27 | 1 | ENSP00000367411.3 | ||||
NPHP4 | ENST00000489180.6 | n.*1054G>C | non_coding_transcript_exon_variant | Exon 26 of 33 | 2 | ENSP00000423747.1 | ||||
NPHP4 | ENST00000378169.7 | n.*2144G>C | 3_prime_UTR_variant | Exon 20 of 27 | 1 | ENSP00000367411.3 | ||||
NPHP4 | ENST00000489180.6 | n.*1054G>C | 3_prime_UTR_variant | Exon 26 of 33 | 2 | ENSP00000423747.1 |
Frequencies
GnomAD3 genomes AF: 0.0163 AC: 2474AN: 152174Hom.: 34 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0145 AC: 3621AN: 249198 AF XY: 0.0146 show subpopulations
GnomAD4 exome AF: 0.0239 AC: 34953AN: 1461428Hom.: 514 Cov.: 31 AF XY: 0.0231 AC XY: 16797AN XY: 726996 show subpopulations
GnomAD4 genome AF: 0.0162 AC: 2474AN: 152292Hom.: 34 Cov.: 33 AF XY: 0.0150 AC XY: 1116AN XY: 74450 show subpopulations
ClinVar
Submissions by phenotype
not specified Benign:2
- -
- -
Kidney disorder Benign:1
- -
Senior-Loken syndrome 4 Benign: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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Nephronophthisis Benign:1
- -
not provided Benign:1
- -
Nephronophthisis 4 Benign: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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at