chr7-128937563-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000652525.1(IRF5):​c.-143T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,132 control chromosomes in the GnomAD database, including 26,359 homozygotes. 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 0.58 ( 26333 hom., cov: 33)
Exomes 𝑓: 0.63 ( 26 hom. )

Consequence

IRF5
ENST00000652525.1 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.114

Publications

9 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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IRF5XM_011516160.2 linkc.-283T>C 5_prime_UTR_variant Exon 1 of 9 XP_011514462.1 Q13568-2C9JAU6
IRF5XM_047420338.1 linkc.-283T>C 5_prime_UTR_variant Exon 1 of 9 XP_047276294.1
IRF5NM_001347928.2 linkc.-12+298T>C intron_variant Intron 1 of 8 NP_001334857.1 Q13568-2A0A0G2USB5C9JAU6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IRF5ENST00000652525.1 linkc.-143T>C 5_prime_UTR_variant Exon 1 of 2 ENSP00000498293.1 A0A0G2UM11
IRF5ENST00000489702.6 linkc.-283T>C upstream_gene_variant 5 ENSP00000418037.2 Q13568-2
IRF5ENST00000700148.1 linkn.-220T>C upstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.583
AC:
88510
AN:
151874
Hom.:
26318
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.522
Gnomad AMI
AF:
0.616
Gnomad AMR
AF:
0.527
Gnomad ASJ
AF:
0.734
Gnomad EAS
AF:
0.355
Gnomad SAS
AF:
0.604
Gnomad FIN
AF:
0.646
Gnomad MID
AF:
0.671
Gnomad NFE
AF:
0.629
Gnomad OTH
AF:
0.607
GnomAD4 exome
AF:
0.634
AC:
90
AN:
142
Hom.:
26
Cov.:
0
AF XY:
0.683
AC XY:
71
AN XY:
104
show subpopulations
African (AFR)
AF:
0.500
AC:
1
AN:
2
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AF:
0.500
AC:
1
AN:
2
East Asian (EAS)
AF:
1.00
AC:
2
AN:
2
South Asian (SAS)
AF:
0.500
AC:
1
AN:
2
European-Finnish (FIN)
AF:
0.688
AC:
11
AN:
16
Middle Eastern (MID)
AF:
1.00
AC:
2
AN:
2
European-Non Finnish (NFE)
AF:
0.614
AC:
70
AN:
114
Other (OTH)
AF:
1.00
AC:
2
AN:
2
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<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:
0.583
AC:
88562
AN:
151990
Hom.:
26333
Cov.:
33
AF XY:
0.580
AC XY:
43135
AN XY:
74316
show subpopulations
African (AFR)
AF:
0.522
AC:
21643
AN:
41456
American (AMR)
AF:
0.527
AC:
8041
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.734
AC:
2547
AN:
3468
East Asian (EAS)
AF:
0.356
AC:
1832
AN:
5148
South Asian (SAS)
AF:
0.605
AC:
2917
AN:
4822
European-Finnish (FIN)
AF:
0.646
AC:
6844
AN:
10596
Middle Eastern (MID)
AF:
0.673
AC:
198
AN:
294
European-Non Finnish (NFE)
AF:
0.629
AC:
42706
AN:
67912
Other (OTH)
AF:
0.602
AC:
1273
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
1912
3825
5737
7650
9562
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
760
1520
2280
3040
3800
<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:
0.606
Hom.:
10789
Bravo
AF:
0.570
Asia WGS
AF:
0.476
AC:
1658
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
1.7
DANN
Benign
0.33
PhyloP100
0.11
PromoterAI
-0.022
Neutral

Splicing

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

Publications

Other links and lift over

dbSNP: rs3807135; hg19: chr7-128577617; API