rs782387990
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_001353921.2(ARHGEF9):c.1293G>A(p.Arg431=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,209,483 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.000018 ( 0 hom. 3 hem. )
Consequence
ARHGEF9
NM_001353921.2 synonymous
NM_001353921.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.06
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant X-63655522-C-T is Benign according to our data. Variant chrX-63655522-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 465076.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.06 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000179 (2/111708) while in subpopulation AMR AF= 0.000191 (2/10494). AF 95% confidence interval is 0.0000334. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAdExome4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF9 | NM_001353921.2 | c.1293G>A | p.Arg431= | synonymous_variant | 8/10 | ENST00000671741.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF9 | ENST00000671741.2 | c.1293G>A | p.Arg431= | synonymous_variant | 8/10 | NM_001353921.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111708Hom.: 0 Cov.: 22 AF XY: 0.0000295 AC XY: 1AN XY: 33920
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GnomAD3 exomes AF: 0.0000656 AC: 12AN: 182911Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67555
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GnomAD4 exome AF: 0.0000182 AC: 20AN: 1097775Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 3AN XY: 363353
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GnomAD4 genome ? AF: 0.0000179 AC: 2AN: 111708Hom.: 0 Cov.: 22 AF XY: 0.0000295 AC XY: 1AN XY: 33920
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 16, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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