dbSNP rs41298401: IRF5:c.-12+204C>G (chr7-128938253-C-G) – 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.-12+204C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 152,378 control chromosomes in the GnomAD database, including 284 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 0.036 ( 284 hom., cov: 31)

Exomes 𝑓: 0.043 ( 0 hom. )

Consequence

IRF5
NM_001098629.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.185

Publications

8 publications found

Variant links:

COSMIC-nc: COSV107218922

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=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3 link	c.-12+204C>G		intron_variant	Intron 1 of 8	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.-12+204C>G		intron_variant	Intron 1 of 8	1	NM_001098629.3	ENSP00000349770.5		Q13568-2

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5486

AN:

152098

Hom.:

285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0682

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0330

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.0707

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00544

Gnomad OTH

AF:

0.0316

GnomAD4 exome

AF:

0.0427

AC:

AN:

164

Hom.:

Cov.:

AF XY:

0.0431

AC XY:

AN XY:

116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0147

AC:

AN:

136

Other (OTH)

AF:

0.200

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0361

AC:

5495

AN:

152214

Hom.:

284

Cov.:

AF XY:

0.0383

AC XY:

2848

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0682

AC:

2834

AN:

41548

American (AMR)

AF:

0.0327

AC:

501

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3470

East Asian (EAS)

AF:

0.228

AC:

1171

AN:

5136

South Asian (SAS)

AF:

0.0713

AC:

344

AN:

4822

European-Finnish (FIN)

AF:

0.0138

AC:

146

AN:

10616

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00544

AC:

370

AN:

68000

Other (OTH)

AF:

0.0332

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

249

498

748

997

1246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0221

Hom.:

Bravo

AF:

0.0407

Asia WGS

AF:

0.145

AC:

504

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.18

PromoterAI

0.087

Neutral

(source)

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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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