rs10133301
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_022489.4(INF2):c.2640T>C(p.Asp880=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,612,146 control chromosomes in the GnomAD database, including 585,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.88 ( 59656 hom., cov: 35)
Exomes 𝑓: 0.85 ( 526232 hom. )
Consequence
INF2
NM_022489.4 synonymous
NM_022489.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.25
Genes affected
INF2 (HGNC:23791): (inverted formin 2) This gene represents a member of the formin family of proteins. It is considered a diaphanous formin due to the presence of a diaphanous inhibitory domain located at the N-terminus of the encoded protein. Studies of a similar mouse protein indicate that the protein encoded by this locus may function in polymerization and depolymerization of actin filaments. Mutations at this locus have been associated with focal segmental glomerulosclerosis 5.[provided by RefSeq, Aug 2010]
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=-0.93).
BP6
?
Variant 14-104712857-T-C is Benign according to our data. Variant chr14-104712857-T-C is described in ClinVar as [Benign]. Clinvar id is 261611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104712857-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.24 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INF2 | NM_022489.4 | c.2640T>C | p.Asp880= | synonymous_variant | 18/23 | ENST00000392634.9 | |
INF2 | NM_001031714.4 | c.2640T>C | p.Asp880= | synonymous_variant | 18/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INF2 | ENST00000392634.9 | c.2640T>C | p.Asp880= | synonymous_variant | 18/23 | 5 | NM_022489.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.882 AC: 134253AN: 152184Hom.: 59598 Cov.: 35
GnomAD3 genomes
?
AF:
AC:
134253
AN:
152184
Hom.:
Cov.:
35
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: 0.861 AC: 212235AN: 246426Hom.: 91725 AF XY: 0.855 AC XY: 114975AN XY: 134476
GnomAD3 exomes
AF:
AC:
212235
AN:
246426
Hom.:
AF XY:
AC XY:
114975
AN XY:
134476
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: 0.848 AC: 1238245AN: 1459844Hom.: 526232 Cov.: 72 AF XY: 0.847 AC XY: 615049AN XY: 726154
GnomAD4 exome
AF:
AC:
1238245
AN:
1459844
Hom.:
Cov.:
72
AF XY:
AC XY:
615049
AN XY:
726154
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: 0.882 AC: 134368AN: 152302Hom.: 59656 Cov.: 35 AF XY: 0.880 AC XY: 65550AN XY: 74474
GnomAD4 genome
?
AF:
AC:
134368
AN:
152302
Hom.:
Cov.:
35
AF XY:
AC XY:
65550
AN XY:
74474
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:
3168
AN:
3476
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 15, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 92. Only high quality variants are reported. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Charcot-Marie-Tooth disease dominant intermediate E Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Focal segmental glomerulosclerosis 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 25, 2017 | - - |
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