chr8-1857950-T-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_014629.4(ARHGEF10):c.38-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,594,746 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0035 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0046 ( 37 hom. )
Consequence
ARHGEF10
NM_014629.4 splice_polypyrimidine_tract, intron
NM_014629.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00004788
2
Clinical Significance
Conservation
PhyloP100: 0.213
Genes affected
ARHGEF10 (HGNC:14103): (Rho guanine nucleotide exchange factor 10) This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 8-1857950-T-C is Benign according to our data. Variant chr8-1857950-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 439416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-1857950-T-C is described in Lovd as [Benign]. Variant chr8-1857950-T-C is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd at 529 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF10 | NM_014629.4 | c.38-10T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000349830.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF10 | ENST00000349830.8 | c.38-10T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014629.4 | P4 | |||
ARHGEF10 | ENST00000518288.5 | c.110-10T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
ARHGEF10 | ENST00000520359.5 | c.38-10T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | A2 | ||||
ARHGEF10 | ENST00000398564.5 | c.110-10T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00351 AC: 529AN: 150836Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00389 AC: 976AN: 250758Hom.: 7 AF XY: 0.00434 AC XY: 589AN XY: 135596
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GnomAD4 exome AF: 0.00458 AC: 6615AN: 1443794Hom.: 37 Cov.: 32 AF XY: 0.00463 AC XY: 3325AN XY: 717756
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GnomAD4 genome ? AF: 0.00350 AC: 529AN: 150952Hom.: 1 Cov.: 32 AF XY: 0.00359 AC XY: 265AN XY: 73776
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal dominant slowed nerve conduction velocity Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Oct 09, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 08, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Feb 16, 2016 | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at