7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4BP6_ModerateBA1

The NM_001098629.3(IRF5):​c.572_601delGGCCGCCTACTCTGCAGCCGCCCACTCTGC​(p.Arg191_Leu200del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 18851 hom., cov: 0)
Exomes 𝑓: 0.50 ( 180811 hom. )
Failed GnomAD Quality Control

Consequence

IRF5
NM_001098629.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.736

Publications

11 publications found
Variant links:
Genes affected
IRF5 (HGNC:6120): (interferon regulatory factor 5) This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative promoter use and alternative splicing result in multiple transcript variants, and a 30-nt indel polymorphism (SNP rs60344245) can result in loss of a 10-aa segment. [provided by RefSeq, Dec 2016]
IRF5 Gene-Disease associations (from GenCC):
  • systemic lupus erythematosus
    Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_001098629.3.
BP6
Variant 7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-C is Benign according to our data. Variant chr7-128947297-CACTCTGCAGCCGCCCACTCTGCGGCCGCCT-C is described in ClinVar as [Benign]. Clinvar id is 768201.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IRF5NM_001098629.3 linkc.572_601delGGCCGCCTACTCTGCAGCCGCCCACTCTGC p.Arg191_Leu200del disruptive_inframe_deletion Exon 6 of 9 ENST00000357234.10 NP_001092099.1 Q13568-2B7Z1M2C9JAU6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IRF5ENST00000357234.10 linkc.572_601delGGCCGCCTACTCTGCAGCCGCCCACTCTGC p.Arg191_Leu200del disruptive_inframe_deletion Exon 6 of 9 1 NM_001098629.3 ENSP00000349770.5 Q13568-2

Frequencies

GnomAD3 genomes
AF:
0.495
AC:
75054
AN:
151476
Hom.:
18838
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.532
Gnomad AMI
AF:
0.597
Gnomad AMR
AF:
0.389
Gnomad ASJ
AF:
0.605
Gnomad EAS
AF:
0.468
Gnomad SAS
AF:
0.462
Gnomad FIN
AF:
0.474
Gnomad MID
AF:
0.471
Gnomad NFE
AF:
0.498
Gnomad OTH
AF:
0.500
GnomAD2 exomes
AF:
0.463
AC:
108068
AN:
233398
AF XY:
0.467
show subpopulations
Gnomad AFR exome
AF:
0.521
Gnomad AMR exome
AF:
0.300
Gnomad ASJ exome
AF:
0.585
Gnomad EAS exome
AF:
0.485
Gnomad FIN exome
AF:
0.470
Gnomad NFE exome
AF:
0.492
Gnomad OTH exome
AF:
0.465
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.496
AC:
720257
AN:
1451580
Hom.:
180811
AF XY:
0.496
AC XY:
358146
AN XY:
721776
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.529
AC:
17604
AN:
33270
American (AMR)
AF:
0.315
AC:
13905
AN:
44194
Ashkenazi Jewish (ASJ)
AF:
0.595
AC:
15429
AN:
25910
East Asian (EAS)
AF:
0.481
AC:
19032
AN:
39536
South Asian (SAS)
AF:
0.459
AC:
39239
AN:
85496
European-Finnish (FIN)
AF:
0.476
AC:
24660
AN:
51788
Middle Eastern (MID)
AF:
0.497
AC:
2805
AN:
5648
European-Non Finnish (NFE)
AF:
0.504
AC:
557672
AN:
1105770
Other (OTH)
AF:
0.499
AC:
29911
AN:
59968
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.380
Heterozygous variant carriers
0
20178
40356
60534
80712
100890
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
16206
32412
48618
64824
81030
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.495
AC:
75108
AN:
151594
Hom.:
18851
Cov.:
0
AF XY:
0.490
AC XY:
36268
AN XY:
74040
show subpopulations
African (AFR)
AF:
0.532
AC:
21974
AN:
41298
American (AMR)
AF:
0.388
AC:
5912
AN:
15234
Ashkenazi Jewish (ASJ)
AF:
0.605
AC:
2096
AN:
3464
East Asian (EAS)
AF:
0.469
AC:
2413
AN:
5146
South Asian (SAS)
AF:
0.461
AC:
2211
AN:
4792
European-Finnish (FIN)
AF:
0.474
AC:
4992
AN:
10532
Middle Eastern (MID)
AF:
0.483
AC:
141
AN:
292
European-Non Finnish (NFE)
AF:
0.498
AC:
33778
AN:
67822
Other (OTH)
AF:
0.498
AC:
1049
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.447
Heterozygous variant carriers
0
1868
3736
5603
7471
9339
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
668
1336
2004
2672
3340
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.498
Hom.:
3203

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.74
Mutation Taster
=193/7
polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs60344245; hg19: chr7-128587351; COSMIC: COSV50856661; COSMIC: COSV50856661; API