Genetic Variant ENST00000652525.1: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

new If you want to explore the variant's impact on the transcript ENST00000652525.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652525.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF5	NM_001347928.2		c.-12+298T>C		intron	N/A	NP_001334857.1	Q13568-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IRF5	ENST00000652525.1		c.-143T>C	5_prime_UTR	Exon 1 of 2	ENSP00000498293.1	A0A0G2UM11
IRF5	ENST00000898739.1		c.-12+3965T>C	intron	N/A	ENSP00000568798.1
IRF5	ENST00000489702.6	TSL:5	c.-283T>C	upstream_gene	N/A	ENSP00000418037.2	Q13568-2

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over