22-35067222-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001303508.2(ISX):āc.135T>Cā(p.Asp45Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,610,112 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.011 ( 30 hom., cov: 33)
Exomes š: 0.0013 ( 39 hom. )
Consequence
ISX
NM_001303508.2 synonymous
NM_001303508.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.03
Genes affected
ISX (HGNC:28084): (intestine specific homeobox) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the RAXLX homeobox gene family. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BP6
Variant 22-35067222-T-C is Benign according to our data. Variant chr22-35067222-T-C is described in ClinVar as [Benign]. Clinvar id is 784419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.03 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1687/152228) while in subpopulation AFR AF= 0.038 (1578/41534). AF 95% confidence interval is 0.0364. There are 30 homozygotes in gnomad4. There are 804 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 30 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ISX | NM_001303508.2 | c.135T>C | p.Asp45Asp | synonymous_variant | 2/5 | ENST00000404699.7 | NP_001290437.1 | |
ISX | XM_047441598.1 | c.135T>C | p.Asp45Asp | synonymous_variant | 1/4 | XP_047297554.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ISX | ENST00000404699.7 | c.135T>C | p.Asp45Asp | synonymous_variant | 2/5 | 1 | NM_001303508.2 | ENSP00000386037.1 | ||
ISX | ENST00000308700.6 | c.135T>C | p.Asp45Asp | synonymous_variant | 1/4 | 1 | ENSP00000311492.6 |
Frequencies
GnomAD3 genomes AF: 0.0111 AC: 1685AN: 152110Hom.: 30 Cov.: 33
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GnomAD3 exomes AF: 0.00307 AC: 741AN: 241142Hom.: 11 AF XY: 0.00221 AC XY: 288AN XY: 130292
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GnomAD4 exome AF: 0.00133 AC: 1939AN: 1457884Hom.: 39 Cov.: 40 AF XY: 0.00111 AC XY: 808AN XY: 724766
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GnomAD4 genome AF: 0.0111 AC: 1687AN: 152228Hom.: 30 Cov.: 33 AF XY: 0.0108 AC XY: 804AN XY: 74430
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 20, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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