Genetic Variant NM_001098629.3:c.-11-849C>T (chr7-128941222-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001098629.3(IRF5):c.-11-849C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 152,518 control chromosomes in the GnomAD database, including 29 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 0.015 ( 29 hom., cov: 33)

Exomes 𝑓: 0.028 ( 0 hom. )

Consequence

IRF5
NM_001098629.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

Publications

1 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=-0.97).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0154 (2352/152234) while in subpopulation NFE AF = 0.0235 (1599/68006). AF 95% confidence interval is 0.0226. There are 29 homozygotes in GnomAd4. There are 1164 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 29 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3 link	c.-11-849C>T		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.-11-849C>T		intron_variant	Intron 1 of 8	1	NM_001098629.3	ENSP00000349770.5		Q13568-2

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2353

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00410

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00982

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0101

GnomAD4 exome

AF:

0.0282

AC:

AN:

284

Hom.:

AF XY:

0.0337

AC XY:

AN XY:

208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0800

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0200

AC:

AN:

200

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0154

AC:

2352

AN:

152234

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1164

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00409

AC:

170

AN:

41546

American (AMR)

AF:

0.00981

AC:

150

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00270

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0340

AC:

361

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0235

AC:

1599

AN:

68006

Other (OTH)

AF:

0.00995

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

120

239

359

478

598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00890

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

6.9

(source)

DANN

Benign

0.64

PhyloP100

-1.4

PromoterAI

-0.16

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over