rs4291265
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_004318.4(ASPH):c.1537-116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 727,684 control chromosomes in the GnomAD database, including 23,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.30 ( 9389 hom., cov: 33)
Exomes 𝑓: 0.20 ( 13812 hom. )
Consequence
ASPH
NM_004318.4 intron
NM_004318.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0160
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 8-61553236-T-C is Benign according to our data. Variant chr8-61553236-T-C is described in ClinVar as [Benign]. Clinvar id is 1236010.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASPH | NM_004318.4 | c.1537-116A>G | intron_variant | ENST00000379454.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASPH | ENST00000379454.9 | c.1537-116A>G | intron_variant | 1 | NM_004318.4 | P3 | |||
ASPH | ENST00000541428.5 | c.1450-116A>G | intron_variant | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.304 AC: 46162AN: 151984Hom.: 9372 Cov.: 33
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GnomAD4 exome AF: 0.201 AC: 115697AN: 575582Hom.: 13812 AF XY: 0.198 AC XY: 60257AN XY: 304274
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GnomAD4 genome ? AF: 0.304 AC: 46218AN: 152102Hom.: 9389 Cov.: 33 AF XY: 0.299 AC XY: 22236AN XY: 74384
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at