NM_005544.3:c.3489A>C
Variant names:
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005544.3(IRS1):c.3489A>C(p.Pro1163Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,613,876 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0014 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00099 ( 10 hom. )
Consequence
IRS1
NM_005544.3 synonymous
NM_005544.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.68
Publications
1 publications found
Genes affected
IRS1 (HGNC:6125): (insulin receptor substrate 1) This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 2-226795250-T-G is Benign according to our data. Variant chr2-226795250-T-G is described in ClinVar as [Benign]. Clinvar id is 722785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-6.68 with no splicing effect.
BS2
High AC in GnomAd4 at 217 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IRS1 | NM_005544.3 | c.3489A>C | p.Pro1163Pro | synonymous_variant | Exon 1 of 2 | ENST00000305123.6 | NP_005535.1 | |
IRS1 | XM_047444223.1 | c.3489A>C | p.Pro1163Pro | synonymous_variant | Exon 1 of 2 | XP_047300179.1 | ||
IRS1 | XM_047444224.1 | c.3489A>C | p.Pro1163Pro | synonymous_variant | Exon 1 of 2 | XP_047300180.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IRS1 | ENST00000305123.6 | c.3489A>C | p.Pro1163Pro | synonymous_variant | Exon 1 of 2 | 1 | NM_005544.3 | ENSP00000304895.4 | ||
ENSG00000272622 | ENST00000727652.1 | n.166+410T>G | intron_variant | Intron 1 of 3 | ||||||
ENSG00000272622 | ENST00000727654.1 | n.71+307T>G | intron_variant | Intron 1 of 3 | ||||||
IRS1 | ENST00000498335.1 | n.-4A>C | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00143 AC: 217AN: 151994Hom.: 6 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
217
AN:
151994
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00217 AC: 545AN: 251100 AF XY: 0.00203 show subpopulations
GnomAD2 exomes
AF:
AC:
545
AN:
251100
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000993 AC: 1452AN: 1461764Hom.: 10 Cov.: 41 AF XY: 0.000972 AC XY: 707AN XY: 727186 show subpopulations
GnomAD4 exome
AF:
AC:
1452
AN:
1461764
Hom.:
Cov.:
41
AF XY:
AC XY:
707
AN XY:
727186
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
46
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
85
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
11
AN:
86258
European-Finnish (FIN)
AF:
AC:
885
AN:
53300
Middle Eastern (MID)
AF:
AC:
3
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
341
AN:
1112006
Other (OTH)
AF:
AC:
81
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
94
188
283
377
471
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.00143 AC: 217AN: 152112Hom.: 6 Cov.: 33 AF XY: 0.00214 AC XY: 159AN XY: 74394 show subpopulations
GnomAD4 genome
AF:
AC:
217
AN:
152112
Hom.:
Cov.:
33
AF XY:
AC XY:
159
AN XY:
74394
show subpopulations
African (AFR)
AF:
AC:
2
AN:
41516
American (AMR)
AF:
AC:
4
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
AC:
11
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5148
South Asian (SAS)
AF:
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
AC:
170
AN:
10602
Middle Eastern (MID)
AF:
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
AC:
25
AN:
67956
Other (OTH)
AF:
AC:
5
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
9
18
26
35
44
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational 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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