rs141596938
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_006420.3(ARFGEF2):āc.1398T>Cā(p.Phe466=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,614,188 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00076 ( 2 hom., cov: 32)
Exomes š: 0.000074 ( 1 hom. )
Consequence
ARFGEF2
NM_006420.3 synonymous
NM_006420.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.38
Genes affected
ARFGEF2 (HGNC:15853): (ADP ribosylation factor guanine nucleotide exchange factor 2) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 20-48971327-T-C is Benign according to our data. Variant chr20-48971327-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 128431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.38 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000762 (116/152328) while in subpopulation AFR AF= 0.00277 (115/41578). AF 95% confidence interval is 0.00236. There are 2 homozygotes in gnomad4. There are 55 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.1398T>C | p.Phe466= | synonymous_variant | 10/39 | ENST00000371917.5 | |
ARFGEF2 | NM_001410846.1 | c.1395T>C | p.Phe465= | synonymous_variant | 10/39 | ||
ARFGEF2 | XM_047439832.1 | c.834T>C | p.Phe278= | synonymous_variant | 8/37 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARFGEF2 | ENST00000371917.5 | c.1398T>C | p.Phe466= | synonymous_variant | 10/39 | 1 | NM_006420.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000762 AC: 116AN: 152210Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000223 AC: 56AN: 251460Hom.: 1 AF XY: 0.000162 AC XY: 22AN XY: 135908
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GnomAD4 exome AF: 0.0000739 AC: 108AN: 1461860Hom.: 1 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 727234
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GnomAD4 genome ? AF: 0.000762 AC: 116AN: 152328Hom.: 2 Cov.: 32 AF XY: 0.000738 AC XY: 55AN XY: 74486
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
ARFGEF2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 02, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 03, 2014 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 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