chr5-73753111-A-G
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001177693.2(ARHGEF28):c.384A>G(p.Ala128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 1,592,358 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00066 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 3 hom. )
Consequence
ARHGEF28
NM_001177693.2 synonymous
NM_001177693.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.33
Genes affected
ARHGEF28 (HGNC:30322): (Rho guanine nucleotide exchange factor 28) This gene encodes a member of the Rho guanine nucleotide exchange factor family. The encoded protein interacts with low molecular weight neurofilament mRNA and may be involved in the formation of amyotrophic lateral sclerosis neurofilament aggregates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-1.01).
BP6
?
Variant 5-73753111-A-G is Benign according to our data. Variant chr5-73753111-A-G is described in ClinVar as [Benign]. Clinvar id is 713966.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-6.33 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF28 | NM_001177693.2 | c.384A>G | p.Ala128= | synonymous_variant | 4/36 | ENST00000513042.7 | |
ARHGEF28 | NM_001080479.3 | c.384A>G | p.Ala128= | synonymous_variant | 4/37 | ||
ARHGEF28 | NM_001388078.1 | c.384A>G | p.Ala128= | synonymous_variant | 4/35 | ||
ARHGEF28 | NM_001388076.1 | c.181+3127A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF28 | ENST00000513042.7 | c.384A>G | p.Ala128= | synonymous_variant | 4/36 | 5 | NM_001177693.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000651 AC: 99AN: 152188Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00177 AC: 399AN: 225972Hom.: 2 AF XY: 0.00134 AC XY: 162AN XY: 121046
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GnomAD4 exome AF: 0.000354 AC: 510AN: 1440052Hom.: 3 Cov.: 31 AF XY: 0.000279 AC XY: 199AN XY: 713930
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GnomAD4 genome ? AF: 0.000657 AC: 100AN: 152306Hom.: 1 Cov.: 32 AF XY: 0.000738 AC XY: 55AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 20, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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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