Genetic Variant IRF5:c.-143T>C (chr7-128937563-T-C) – ACMG Classification: Benign (-12 pts)

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

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

IRF5 links:

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	Effect	Exon rank	Protein	UniProt
IRF5	XM_011516160.2 link	c.-283T>C	5_prime_UTR_variant	Exon 1 of 9	XP_011514462.1	Q13568-2C9JAU6
IRF5	XM_047420338.1 link	c.-283T>C	5_prime_UTR_variant	Exon 1 of 9	XP_047276294.1
IRF5	NM_001347928.2 link	c.-12+298T>C	intron_variant	Intron 1 of 8	NP_001334857.1	Q13568-2A0A0G2USB5C9JAU6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
IRF5	ENST00000652525.1 link	c.-143T>C	5_prime_UTR_variant	Exon 1 of 2		ENSP00000498293.1	A0A0G2UM11
IRF5	ENST00000489702.6 link	c.-283T>C	upstream_gene_variant		5	ENSP00000418037.2	Q13568-2
IRF5	ENST00000700148.1 link	n.-220T>C	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.583

AC:

88510

AN:

151874

Hom.:

26318

Cov.:

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:

AN:

142

Hom.:

Cov.:

AF XY:

0.683

AC XY:

AN XY:

104

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.688

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.614

AC:

AN:

114

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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.:

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

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

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

(source)

DANN

Benign

0.33

PhyloP100

0.11

PromoterAI

-0.022

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over