rs77465715
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_014425.5(INVS):āc.1284T>Cā(p.His428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000647 in 1,613,976 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0034 ( 1 hom., cov: 32)
Exomes š: 0.00036 ( 5 hom. )
Consequence
INVS
NM_014425.5 synonymous
NM_014425.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.109
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 9-100252956-T-C is Benign according to our data. Variant chr9-100252956-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 260406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-100252956-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.109 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00344 (524/152288) while in subpopulation AFR AF= 0.0119 (496/41556). AF 95% confidence interval is 0.0111. There are 1 homozygotes in gnomad4. There are 253 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INVS | NM_014425.5 | c.1284T>C | p.His428= | synonymous_variant | 10/17 | ENST00000262457.7 | |
INVS | NM_001318381.2 | c.996T>C | p.His332= | synonymous_variant | 11/18 | ||
INVS | NM_001318382.2 | c.306T>C | p.His102= | synonymous_variant | 10/17 | ||
INVS | NR_134606.2 | n.1482T>C | non_coding_transcript_exon_variant | 10/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INVS | ENST00000262457.7 | c.1284T>C | p.His428= | synonymous_variant | 10/17 | 1 | NM_014425.5 | A2 | |
INVS | ENST00000262456.6 | c.1284T>C | p.His428= | synonymous_variant | 10/18 | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00338 AC: 514AN: 152170Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
514
AN:
152170
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: 0.000856 AC: 215AN: 251168Hom.: 0 AF XY: 0.000663 AC XY: 90AN XY: 135728
GnomAD3 exomes
AF:
AC:
215
AN:
251168
Hom.:
AF XY:
AC XY:
90
AN XY:
135728
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: 0.000356 AC: 520AN: 1461688Hom.: 5 Cov.: 32 AF XY: 0.000315 AC XY: 229AN XY: 727150
GnomAD4 exome
AF:
AC:
520
AN:
1461688
Hom.:
Cov.:
32
AF XY:
AC XY:
229
AN XY:
727150
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 ? AF: 0.00344 AC: 524AN: 152288Hom.: 1 Cov.: 32 AF XY: 0.00340 AC XY: 253AN XY: 74476
GnomAD4 genome
?
AF:
AC:
524
AN:
152288
Hom.:
Cov.:
32
AF XY:
AC XY:
253
AN XY:
74476
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:
6
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Kidney disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 06, 2017 | - - |
Nephronophthisis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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