X-108735112-T-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001379150.1(IRS4):c.1233A>G(p.Arg411Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 111,451 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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 0.0000090 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control
Consequence
IRS4
NM_001379150.1 synonymous
NM_001379150.1 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.435
Publications
4 publications found
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]
IRS4 Gene-Disease associations (from GenCC):
- hypothyroidism, congenital, nongoitrous, 9Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP7
Synonymous conserved (PhyloP=0.435 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| IRS4 | NM_001379150.1 | c.1233A>G | p.Arg411Arg | synonymous_variant | Exon 1 of 2 | ENST00000372129.4 | NP_001366079.1 | |
| IRS4 | NM_001440817.1 | c.1233A>G | p.Arg411Arg | synonymous_variant | Exon 1 of 3 | NP_001427746.1 | ||
| IRS4 | NM_003604.2 | c.1233A>G | p.Arg411Arg | synonymous_variant | Exon 1 of 1 | NP_003595.1 | ||
| IRS4 | XM_006724713.4 | c.1233A>G | p.Arg411Arg | synonymous_variant | Exon 1 of 2 | XP_006724776.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| IRS4 | ENST00000372129.4 | c.1233A>G | p.Arg411Arg | synonymous_variant | Exon 1 of 2 | 6 | NM_001379150.1 | ENSP00000361202.3 | ||
| IRS4 | ENST00000564206.2 | c.1233A>G | p.Arg411Arg | synonymous_variant | Exon 1 of 1 | 6 | ENSP00000505547.1 |
Frequencies
GnomAD3 genomes 0.00000897 AC: 1AN: 111451Hom.: 0 Cov.: 22 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
111451
Hom.:
Cov.:
22
Gnomad AFR
AF:
Gnomad AMI
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Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.00000548 AC: 1AN: 182632 AF XY: 0.0000149 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
182632
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000182 AC: 2AN: 1098054Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 1AN XY: 363446 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2
AN:
1098054
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
363446
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26403
American (AMR)
AF:
AC:
0
AN:
35192
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19385
East Asian (EAS)
AF:
AC:
0
AN:
30206
South Asian (SAS)
AF:
AC:
0
AN:
54147
European-Finnish (FIN)
AF:
AC:
0
AN:
40376
Middle Eastern (MID)
AF:
AC:
0
AN:
4137
European-Non Finnish (NFE)
AF:
AC:
1
AN:
842111
Other (OTH)
AF:
AC:
1
AN:
46097
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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>80
Age
GnomAD4 genome 0.00000897 AC: 1AN: 111451Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33665 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
111451
Hom.:
Cov.:
22
AF XY:
AC XY:
0
AN XY:
33665
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30618
American (AMR)
AF:
AC:
0
AN:
10575
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
2642
East Asian (EAS)
AF:
AC:
0
AN:
3531
South Asian (SAS)
AF:
AC:
0
AN:
2671
European-Finnish (FIN)
AF:
AC:
0
AN:
6007
Middle Eastern (MID)
AF:
AC:
0
AN:
235
European-Non Finnish (NFE)
AF:
AC:
0
AN:
53012
Other (OTH)
AF:
AC:
0
AN:
1479
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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