rs186710481
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_000293.3(PHKB):c.2766-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,614,014 control chromosomes in the GnomAD database, including 1 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_000293.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PHKB | NM_000293.3 | c.2766-8T>C | splice_region_variant, intron_variant | ENST00000323584.10 | NP_000284.1 | |||
PHKB | NM_001363837.1 | c.2766-8T>C | splice_region_variant, intron_variant | NP_001350766.1 | ||||
PHKB | NM_001031835.3 | c.2745-8T>C | splice_region_variant, intron_variant | NP_001027005.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000430 AC: 108AN: 251038Hom.: 0 AF XY: 0.000413 AC XY: 56AN XY: 135654
GnomAD4 exome AF: 0.000107 AC: 156AN: 1461692Hom.: 1 Cov.: 31 AF XY: 0.000107 AC XY: 78AN XY: 727160
GnomAD4 genome AF: 0.000177 AC: 27AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74494
ClinVar
Submissions by phenotype
Glycogen storage disease IXb Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at