rs199624091
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004984.4(KIF5A):c.714+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,611,082 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004984.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF5A | NM_004984.4 | c.714+8G>A | splice_region_variant, intron_variant | ENST00000455537.7 | |||
KIF5A | NM_001354705.2 | c.447+8G>A | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF5A | ENST00000455537.7 | c.714+8G>A | splice_region_variant, intron_variant | 1 | NM_004984.4 | P1 | |||
KIF5A | ENST00000286452.5 | c.447+8G>A | splice_region_variant, intron_variant | 2 | |||||
KIF5A | ENST00000674619.1 | c.714+8G>A | splice_region_variant, intron_variant | ||||||
KIF5A | ENST00000676457.1 | c.609+8G>A | splice_region_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00140 AC: 212AN: 151184Hom.: 0 Cov.: 27
GnomAD3 exomes AF: 0.00121 AC: 300AN: 248916Hom.: 0 AF XY: 0.00109 AC XY: 147AN XY: 134488
GnomAD4 exome AF: 0.00163 AC: 2373AN: 1459794Hom.: 2 Cov.: 34 AF XY: 0.00151 AC XY: 1097AN XY: 726168
GnomAD4 genome ? AF: 0.00140 AC: 212AN: 151288Hom.: 0 Cov.: 27 AF XY: 0.00149 AC XY: 110AN XY: 73894
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 02, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | KIF5A: BP4, BS1 - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 19, 2019 | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hereditary spastic paraplegia 10 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. - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 01, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at