9-100104505-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_014425.5(INVS):c.-17C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,580,822 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )
Consequence
INVS
NM_014425.5 5_prime_UTR_premature_start_codon_gain
NM_014425.5 5_prime_UTR_premature_start_codon_gain
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.541
Genes affected
INVS (HGNC:17870): (inversin) This gene encodes a protein containing multiple ankyrin domains and two IQ calmodulin-binding domains. The encoded protein may function in renal tubular development and function, and in left-right axis determination. This protein interacts with nephrocystin and infers a connection between primary cilia function and left-right axis determination. A similar protein in mice interacts with calmodulin. Mutations in this gene have been associated with nephronophthisis type 2. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 9-100104505-C-T is Benign according to our data. Variant chr9-100104505-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 95593.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00177 (270/152276) while in subpopulation AFR AF= 0.00619 (257/41538). AF 95% confidence interval is 0.00557. There are 0 homozygotes in gnomad4. There are 121 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| INVS | NM_014425.5 | c.-17C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 2 of 17 | ENST00000262457.7 | NP_055240.2 | ||
| INVS | NM_014425.5 | c.-17C>T | 5_prime_UTR_variant | Exon 2 of 17 | ENST00000262457.7 | NP_055240.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| INVS | ENST00000262457 | c.-17C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 2 of 17 | 1 | NM_014425.5 | ENSP00000262457.2 | |||
| INVS | ENST00000262457 | c.-17C>T | 5_prime_UTR_variant | Exon 2 of 17 | 1 | NM_014425.5 | ENSP00000262457.2 |
Frequencies
GnomAD3 genomes 0.00177 AC: 269AN: 152158Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
269
AN:
152158
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000531 AC: 133AN: 250314Hom.: 0 AF XY: 0.000414 AC XY: 56AN XY: 135316
GnomAD3 exomes
AF:
AC:
133
AN:
250314
Hom.:
AF XY:
AC XY:
56
AN XY:
135316
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000210 AC: 300AN: 1428546Hom.: 1 Cov.: 27 AF XY: 0.000196 AC XY: 140AN XY: 712940
GnomAD4 exome
AF:
AC:
300
AN:
1428546
Hom.:
Cov.:
27
AF XY:
AC XY:
140
AN XY:
712940
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome 0.00177 AC: 270AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.00162 AC XY: 121AN XY: 74468
GnomAD4 genome
AF:
AC:
270
AN:
152276
Hom.:
Cov.:
32
AF XY:
AC XY:
121
AN XY:
74468
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2
AN:
3478
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Aug 16, 2018
Eurofins Ntd Llc (ga)
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Infantile nephronophthisis Benign:1
Apr 28, 2017
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at