chr1-6467651-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_020631.6(PLEKHG5):c.3012-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 1,518,896 control chromosomes in the GnomAD database, including 423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.017 ( 41 hom., cov: 33)
Exomes 𝑓: 0.022 ( 382 hom. )
Consequence
PLEKHG5
NM_020631.6 intron
NM_020631.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.81
Genes affected
PLEKHG5 (HGNC:29105): (pleckstrin homology and RhoGEF domain containing G5) This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 1-6467651-G-A is Benign according to our data. Variant chr1-6467651-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 676978.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-6467651-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0166 (2527/152192) while in subpopulation NFE AF= 0.0256 (1738/67968). AF 95% confidence interval is 0.0246. There are 41 homozygotes in gnomad4. There are 1182 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 41 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHG5 | NM_020631.6 | c.3012-79C>T | intron_variant | ENST00000377728.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHG5 | ENST00000377728.8 | c.3012-79C>T | intron_variant | 2 | NM_020631.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0166 AC: 2528AN: 152074Hom.: 41 Cov.: 33
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GnomAD4 exome AF: 0.0216 AC: 29527AN: 1366704Hom.: 382 Cov.: 21 AF XY: 0.0212 AC XY: 14519AN XY: 684794
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely 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. - |
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