3-128795218-T-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004637.6(RAB7A):c.-8-142T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 745,182 control chromosomes in the GnomAD database, including 1,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.053 ( 230 hom., cov: 31)
Exomes 𝑓: 0.051 ( 1006 hom. )
Consequence
RAB7A
NM_004637.6 intron
NM_004637.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.58
Genes affected
RAB7A (HGNC:9788): (RAB7A, member RAS oncogene family) RAB family members are small, RAS-related GTP-binding proteins that are important regulators of vesicular transport. Each RAB protein targets multiple proteins that act in exocytic / endocytic pathways. This gene encodes a RAB family member that regulates vesicle traffic in the late endosomes and also from late endosomes to lysosomes. This encoded protein is also involved in the cellular vacuolation of the VacA cytotoxin of Helicobacter pylori. Mutations at highly conserved amino acid residues in this gene have caused some forms of Charcot-Marie-Tooth (CMT) type 2 neuropathies. [provided by RefSeq, Jul 2008]
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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=-0.98).
BP6
Variant 3-128795218-T-G is Benign according to our data. Variant chr3-128795218-T-G is described in ClinVar as [Benign]. Clinvar id is 674517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAB7A | NM_004637.6 | c.-8-142T>G | intron_variant | ENST00000265062.8 | NP_004628.4 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0534 AC: 8119AN: 152114Hom.: 230 Cov.: 31
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GnomAD4 exome AF: 0.0508 AC: 30132AN: 592950Hom.: 1006 Cov.: 7 AF XY: 0.0482 AC XY: 15408AN XY: 319746
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GnomAD4 genome AF: 0.0535 AC: 8137AN: 152232Hom.: 230 Cov.: 31 AF XY: 0.0527 AC XY: 3923AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2018 | 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 | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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