chrX-108733240-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001379150.1(IRS4):c.3105C>T(p.Ala1035=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,210,095 control chromosomes in the GnomAD database, including 26 homozygotes. There are 666 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.011 ( 13 hom., 323 hem., cov: 23)
Exomes 𝑓: 0.0012 ( 13 hom. 343 hem. )
Consequence
IRS4
NM_001379150.1 synonymous
NM_001379150.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.706
Genes affected
IRS4 (HGNC:6128): (insulin receptor substrate 4) IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein has been shown to associate with cytoplasmic signalling molecules that contain SH2 domains. The IRS4 protein is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation.. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant X-108733240-G-A is Benign according to our data. Variant chrX-108733240-G-A is described in ClinVar as [Benign]. Clinvar id is 716036.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.706 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1183/111863) while in subpopulation AFR AF= 0.0368 (1134/30789). AF 95% confidence interval is 0.0351. There are 13 homozygotes in gnomad4. There are 323 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 13 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRS4 | NM_001379150.1 | c.3105C>T | p.Ala1035= | synonymous_variant | 1/2 | ENST00000372129.4 | |
IRS4 | NM_003604.2 | c.3105C>T | p.Ala1035= | synonymous_variant | 1/1 | ||
IRS4 | XM_011531061.2 | c.3105C>T | p.Ala1035= | synonymous_variant | 1/3 | ||
IRS4 | XM_006724713.4 | c.3105C>T | p.Ala1035= | synonymous_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRS4 | ENST00000372129.4 | c.3105C>T | p.Ala1035= | synonymous_variant | 1/2 | NM_001379150.1 | A2 | ||
IRS4 | ENST00000564206.2 | c.3105C>T | p.Ala1035= | synonymous_variant | 1/1 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.0105 AC: 1177AN: 111810Hom.: 13 Cov.: 23 AF XY: 0.00945 AC XY: 321AN XY: 33970
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GnomAD3 exomes AF: 0.00312 AC: 572AN: 183503Hom.: 4 AF XY: 0.00230 AC XY: 156AN XY: 67935
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GnomAD4 exome AF: 0.00115 AC: 1268AN: 1098232Hom.: 13 Cov.: 32 AF XY: 0.000943 AC XY: 343AN XY: 363588
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GnomAD4 genome ? AF: 0.0106 AC: 1183AN: 111863Hom.: 13 Cov.: 23 AF XY: 0.00949 AC XY: 323AN XY: 34033
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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 | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at