dbSNP rs10954214: IRF5:c.*761C>T (chr7-128949579-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001098629.3(IRF5):c.*761C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,924 control chromosomes in the GnomAD database, including 31,083 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 0.64 ( 31076 hom., cov: 31)

Exomes 𝑓: 0.66 ( 7 hom. )

Consequence

IRF5
NM_001098629.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.665

Publications

17 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=-0.48).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3 link	c.*761C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000357234.10	NP_001092099.1	Q13568-2B7Z1M2C9JAU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10 link	c.*761C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_001098629.3	ENSP00000349770.5		Q13568-2

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96577

AN:

151774

Hom.:

31050

Cov.:

show subpopulations

Gnomad AFR

AF:

0.593

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.755

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.689

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.649

GnomAD4 exome

AF:

0.656

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.625

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.636

AC:

96647

AN:

151892

Hom.:

31076

Cov.:

AF XY:

0.637

AC XY:

47302

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.593

AC:

24557

AN:

41400

American (AMR)

AF:

0.563

AC:

8604

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.755

AC:

2621

AN:

3472

East Asian (EAS)

AF:

0.558

AC:

2872

AN:

5144

South Asian (SAS)

AF:

0.690

AC:

3320

AN:

4814

European-Finnish (FIN)

AF:

0.734

AC:

7734

AN:

10538

Middle Eastern (MID)

AF:

0.704

AC:

207

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44760

AN:

67938

Other (OTH)

AF:

0.646

AC:

1363

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1795

3590

5384

7179

8974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.633

Hom.:

6291

Bravo

AF:

0.623

Asia WGS

AF:

0.629

AC:

2189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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rs10954214

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