rs782366734
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1
The NM_001353921.2(ARHGEF9):c.583-8_583-7insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,166,201 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000085 ( 0 hom. 2 hem. )
Consequence
ARHGEF9
NM_001353921.2 splice_region, splice_polypyrimidine_tract, intron
NM_001353921.2 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0570
Genes affected
ARHGEF9 (HGNC:14561): (Cdc42 guanine nucleotide exchange factor 9) The protein encoded by this gene is a Rho-like GTPase that switches between the active (GTP-bound) state and inactive (GDP-bound) state to regulate CDC42 and other genes. This brain-specific protein also acts as an adaptor protein for the recruitment of gephyrin and together these proteins facilitate receceptor recruitement in GABAnergic and glycinergic synapses. Defects in this gene are the cause of startle disease with epilepsy (STHEE), also known as hyperekplexia with epilepsy, as well as several other types of cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
?
Variant X-63678579-G-GA is Benign according to our data. Variant chrX-63678579-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 533664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000027 (3/111112) while in subpopulation AFR AF= 0.000098 (3/30597). AF 95% confidence interval is 0.000026. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF9 | NM_001353921.2 | c.583-8_583-7insT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000671741.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF9 | ENST00000671741.2 | c.583-8_583-7insT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_001353921.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000270 AC: 3AN: 111112Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33462
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GnomAD3 exomes AF: 0.0000143 AC: 2AN: 139666Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 42310
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GnomAD4 exome AF: 0.00000853 AC: 9AN: 1055089Hom.: 0 Cov.: 27 AF XY: 0.00000604 AC XY: 2AN XY: 331229
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GnomAD4 genome ? AF: 0.0000270 AC: 3AN: 111112Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33462
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 16, 2018 | 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. - |
Developmental and epileptic encephalopathy, 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | - - |
Computational scores
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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