15-90452853-C-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_003870.4(IQGAP1):c.1241C>A(p.Pro414His) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
IQGAP1
NM_003870.4 missense
NM_003870.4 missense
Scores
8
3
8
Clinical Significance
Conservation
PhyloP100: 6.08
Genes affected
IQGAP1 (HGNC:6110): (IQ motif containing GTPase activating protein 1) This gene encodes a member of the IQGAP family. The protein contains four IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. It interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. Expression of the protein is upregulated by gene amplification in two gastric cancer cell lines. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.813
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQGAP1 | NM_003870.4 | c.1241C>A | p.Pro414His | missense_variant | 12/38 | ENST00000268182.10 | |
IQGAP1 | XM_047433204.1 | c.1241C>A | p.Pro414His | missense_variant | 12/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQGAP1 | ENST00000268182.10 | c.1241C>A | p.Pro414His | missense_variant | 12/38 | 1 | NM_003870.4 | P1 | |
IQGAP1 | ENST00000560738.1 | c.107-13194C>A | intron_variant | 5 | |||||
IQGAP1 | ENST00000633485.1 | c.1241C>A | p.Pro414His | missense_variant, NMD_transcript_variant | 12/39 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251176Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135750
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461836Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727218
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74282
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2022 | The c.1241C>A (p.P414H) alteration is located in exon 12 (coding exon 12) of the IQGAP1 gene. This alteration results from a C to A substitution at nucleotide position 1241, causing the proline (P) at amino acid position 414 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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