chr7-102070411-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_181552.4(CUX1):c.262G>A(p.Val88Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00365 in 1,608,414 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0038 ( 19 hom. )
Consequence
CUX1
NM_181552.4 missense
NM_181552.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 9.23
Genes affected
CUX1 (HGNC:2557): (cut like homeobox 1) The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It may regulate gene expression, morphogenesis, and differentiation and it may also play a role in the cell cycle progession. Several alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, CUX1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011179209).
BP6
?
Variant 7-102070411-G-A is Benign according to our data. Variant chr7-102070411-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 709065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00212 (323/152238) while in subpopulation NFE AF= 0.0037 (252/68024). AF 95% confidence interval is 0.00333. There are 1 homozygotes in gnomad4. There are 130 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 321 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUX1 | NM_181552.4 | c.262G>A | p.Val88Ile | missense_variant | 4/24 | ENST00000292535.12 | |
CUX1 | NM_001913.5 | c.295G>A | p.Val99Ile | missense_variant | 4/23 | ENST00000622516.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUX1 | ENST00000292535.12 | c.262G>A | p.Val88Ile | missense_variant | 4/24 | 1 | NM_181552.4 | A2 | |
CUX1 | ENST00000622516.6 | c.295G>A | p.Val99Ile | missense_variant | 4/23 | 1 | NM_001913.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00211 AC: 321AN: 152120Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00203 AC: 494AN: 243800Hom.: 1 AF XY: 0.00218 AC XY: 288AN XY: 132174
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GnomAD4 exome AF: 0.00381 AC: 5554AN: 1456176Hom.: 19 Cov.: 31 AF XY: 0.00377 AC XY: 2731AN XY: 724384
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Asia WGS
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | CUX1: BS1 - |
CUX1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 10, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;D;.;D;D;D;D;D;.;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;N;N;.;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;.;.;T;T;.;T;D;T;D;D;D;D;D
Sift4G
Benign
T;.;.;T;T;T;T;T;T;T;T;T;T;T
Polyphen
P;.;.;P;.;P;.;D;.;D;D;.;.;.
Vest4
MVP
MPC
0.45
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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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