9-100104623-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_014425.5(INVS):c.102C>T(p.Ile34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000999 in 1,607,312 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0051 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00057 ( 11 hom. )
Consequence
INVS
NM_014425.5 synonymous
NM_014425.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 9-100104623-C-T is Benign according to our data. Variant chr9-100104623-C-T is described in ClinVar as [Benign]. Clinvar id is 167194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00512 (780/152232) while in subpopulation AFR AF= 0.0178 (740/41546). AF 95% confidence interval is 0.0167. There are 2 homozygotes in gnomad4. There are 351 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INVS | NM_014425.5 | c.102C>T | p.Ile34= | synonymous_variant | 2/17 | ENST00000262457.7 | NP_055240.2 | |
INVS | NM_001318381.2 | c.-275C>T | 5_prime_UTR_variant | 2/18 | NP_001305310.1 | |||
INVS | NM_001318382.2 | c.-888C>T | 5_prime_UTR_variant | 2/17 | NP_001305311.1 | |||
INVS | NR_134606.2 | n.300C>T | non_coding_transcript_exon_variant | 2/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INVS | ENST00000262457.7 | c.102C>T | p.Ile34= | synonymous_variant | 2/17 | 1 | NM_014425.5 | ENSP00000262457 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00511 AC: 778AN: 152114Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00148 AC: 371AN: 251412Hom.: 1 AF XY: 0.00110 AC XY: 150AN XY: 135884
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GnomAD4 exome AF: 0.000567 AC: 825AN: 1455080Hom.: 11 Cov.: 28 AF XY: 0.000490 AC XY: 355AN XY: 724296
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GnomAD4 genome AF: 0.00512 AC: 780AN: 152232Hom.: 2 Cov.: 32 AF XY: 0.00472 AC XY: 351AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 17, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Nephronophthisis Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at