1-220151708-C-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_012414.4(RAB3GAP2):āc.3924G>Cā(p.Thr1308=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,612,084 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0033 ( 4 hom., cov: 32)
Exomes š: 0.00034 ( 3 hom. )
Consequence
RAB3GAP2
NM_012414.4 synonymous
NM_012414.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.95
Genes affected
RAB3GAP2 (HGNC:17168): (RAB3 GTPase activating non-catalytic protein subunit 2) The protein encoded by this gene belongs to the RAB3 protein family, members of which are involved in regulated exocytosis of neurotransmitters and hormones. This protein forms the Rab3 GTPase-activating complex with RAB3GAP1, where it constitutes the regulatory subunit, whereas the latter functions as the catalytic subunit. This gene has the highest level of expression in the brain, consistent with it having a key role in neurodevelopment. Mutations in this gene are associated with Martsolf syndrome.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 1-220151708-C-G is Benign according to our data. Variant chr1-220151708-C-G is described in ClinVar as [Benign]. Clinvar id is 211988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-220151708-C-G is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00327 (498/152232) while in subpopulation AFR AF= 0.0117 (485/41536). AF 95% confidence interval is 0.0108. There are 4 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAB3GAP2 | NM_012414.4 | c.3924G>C | p.Thr1308= | synonymous_variant | 34/35 | ENST00000358951.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAB3GAP2 | ENST00000358951.7 | c.3924G>C | p.Thr1308= | synonymous_variant | 34/35 | 1 | NM_012414.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00325 AC: 494AN: 152114Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.000832 AC: 209AN: 251310Hom.: 0 AF XY: 0.000560 AC XY: 76AN XY: 135806
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GnomAD4 exome AF: 0.000341 AC: 498AN: 1459852Hom.: 3 Cov.: 31 AF XY: 0.000282 AC XY: 205AN XY: 726382
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GnomAD4 genome AF: 0.00327 AC: 498AN: 152232Hom.: 4 Cov.: 32 AF XY: 0.00336 AC XY: 250AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 18, 2015 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 03, 2015 | - - |
Warburg micro syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Martsolf syndrome;C3280214:Warburg micro syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Martsolf syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
RAB3GAP2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 03, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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