chr8-61503516-C-CAGAA
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_004318.4(ASPH):c.2127-8_2127-7insTTCT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000825 in 1,454,146 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000083 ( 0 hom. )
Consequence
ASPH
NM_004318.4 splice_region, splice_polypyrimidine_tract, intron
NM_004318.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.25
Genes affected
ASPH (HGNC:757): (aspartate beta-hydroxylase) This gene is thought to play an important role in calcium homeostasis. The gene is expressed from two promoters and undergoes extensive alternative splicing. The encoded set of proteins share varying amounts of overlap near their N-termini but have substantial variations in their C-terminal domains resulting in distinct functional properties. The longest isoforms (a and f) include a C-terminal Aspartyl/Asparaginyl beta-hydroxylase domain that hydroxylates aspartic acid or asparagine residues in the epidermal growth factor (EGF)-like domains of some proteins, including protein C, coagulation factors VII, IX, and X, and the complement factors C1R and C1S. Other isoforms differ primarily in the C-terminal sequence and lack the hydroxylase domain, and some have been localized to the endoplasmic and sarcoplasmic reticulum. Some of these isoforms are found in complexes with calsequestrin, triadin, and the ryanodine receptor, and have been shown to regulate calcium release from the sarcoplasmic reticulum. Some isoforms have been implicated in metastasis. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 8-61503516-C-CAGAA is Benign according to our data. Variant chr8-61503516-C-CAGAA is described in ClinVar as [Likely_benign]. Clinvar id is 2694332.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASPH | NM_004318.4 | c.2127-8_2127-7insTTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000379454.9 | NP_004309.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASPH | ENST00000379454.9 | c.2127-8_2127-7insTTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004318.4 | ENSP00000368767 | P3 | |||
ASPH | ENST00000541428.5 | c.2040-8_2040-7insTTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 | ENSP00000437864 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000411 AC: 1AN: 243428Hom.: 0 AF XY: 0.00000759 AC XY: 1AN XY: 131698
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GnomAD4 exome AF: 0.00000825 AC: 12AN: 1454146Hom.: 0 Cov.: 32 AF XY: 0.00000830 AC XY: 6AN XY: 722762
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GnomAD4 genome Cov.: 33
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33
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 | Labcorp Genetics (formerly Invitae), Labcorp | Aug 17, 2023 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at