rs17657775
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000045.4(ARG1):c.131-979G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 149,706 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.033 ( 110 hom., cov: 30)
Consequence
ARG1
NM_000045.4 intron
NM_000045.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.900
Genes affected
ARG1 (HGNC:663): (arginase 1) Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exist (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type I isoform encoded by this gene, is a cytosolic enzyme and expressed predominantly in the liver as a component of the urea cycle. Inherited deficiency of this enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
MED23 (HGNC:2372): (mediator complex subunit 23) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein also acts as a metastasis suppressor. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0326 (4881/149706) while in subpopulation AFR AF= 0.0514 (2083/40508). AF 95% confidence interval is 0.0496. There are 110 homozygotes in gnomad4. There are 2398 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 110 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARG1 | NM_000045.4 | c.131-979G>A | intron_variant | ENST00000368087.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARG1 | ENST00000368087.8 | c.131-979G>A | intron_variant | 1 | NM_000045.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0326 AC: 4871AN: 149604Hom.: 110 Cov.: 30
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0326 AC: 4881AN: 149706Hom.: 110 Cov.: 30 AF XY: 0.0329 AC XY: 2398AN XY: 72850
GnomAD4 genome
?
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2398
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63
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3478
ClinVar
Not reported inComputational scores
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Name
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Prediction
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