rs72624957
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_000883.4(IMPDH1):c.888C>T(p.Ile296=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,612,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )
Consequence
IMPDH1
NM_000883.4 synonymous
NM_000883.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.504
Genes affected
IMPDH1 (HGNC:6052): (inosine monophosphate dehydrogenase 1) The protein encoded by this gene acts as a homotetramer to regulate cell growth. The encoded protein is an enzyme that catalyzes the synthesis of xanthine monophosphate (XMP) from inosine-5'-monophosphate (IMP). This is the rate-limiting step in the de novo synthesis of guanine nucleotides. Defects in this gene are a cause of retinitis pigmentosa type 10 (RP10). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
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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=-0.47).
BP6
?
Variant 7-128398600-G-A is Benign according to our data. Variant chr7-128398600-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 358877.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}. Variant chr7-128398600-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.504 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000238 (348/1460452) while in subpopulation MID AF= 0.00503 (29/5764). AF 95% confidence interval is 0.0036. There are 0 homozygotes in gnomad4_exome. There are 167 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 46 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IMPDH1 | NM_000883.4 | c.888C>T | p.Ile296= | synonymous_variant | 10/17 | ENST00000338791.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IMPDH1 | ENST00000338791.11 | c.888C>T | p.Ile296= | synonymous_variant | 10/17 | 2 | NM_000883.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000302 AC: 46AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000215 AC: 54AN: 250914Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135666
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GnomAD4 exome AF: 0.000238 AC: 348AN: 1460452Hom.: 0 Cov.: 31 AF XY: 0.000230 AC XY: 167AN XY: 726340
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GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74486
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Leber congenital amaurosis 11 Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Retinitis pigmentosa Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
Computational scores
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Name
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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