NM_001098629.3:c.195+10G>A

Variant names:

• chr7-128942286-G-A
• rs183734949
• NM_001098629.3:c.195+10G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_001098629.3(IRF5):​c.195+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,603,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.215
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-128942286-G-A is Benign according to our data. Variant chr7-128942286-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3051361.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098629.3. 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_001098629.3	MANE Select	c.195+10G>A		intron	N/A	NP_001092099.1	Q13568-2
	IRF5	NM_001347928.2		c.195+10G>A		intron	N/A	NP_001334857.1	Q13568-2
	IRF5	NM_001364314.2		c.195+10G>A		intron	N/A	NP_001351243.1	Q13568-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF5	ENST00000357234.10	TSL:1 MANE Select	c.195+10G>A		intron	N/A	ENSP00000349770.5	Q13568-2
	IRF5	ENST00000402030.6	TSL:1	c.195+10G>A		intron	N/A	ENSP00000385352.2	Q13568-1
	IRF5	ENST00000477535.5	TSL:1	c.195+10G>A		intron	N/A	ENSP00000419950.1	Q13568-5

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00396

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000371 AC: 90 AN: 242316 AF XY: 0.000313

Gnomad AFR exome AF: 0.00468

Gnomad AMR exome AF: 0.000297

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000461

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000136 AC: 198 AN: 1450808 Hom.: 0 Cov.: 31 AF XY: 0.000126 AC XY: 91 AN XY: 720478

African (AFR) AF: 0.00422 AC: 140 AN: 33196

American (AMR) AF: 0.000227 AC: 10 AN: 44056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25660

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39324

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53084

Middle Eastern (MID) AF: 0.000185 AC: 1 AN: 5394

European-Non Finnish (NFE) AF: 0.0000281 AC: 31 AN: 1104846

Other (OTH) AF: 0.000234 AC: 14 AN: 59822

GnomAD4 genome AF: 0.00119 AC: 181 AN: 152294 Hom.: 0 Cov.: 33 AF XY: 0.00128 AC XY: 95 AN XY: 74476

African (AFR) AF: 0.00395 AC: 164 AN: 41556

American (AMR) AF: 0.000588 AC: 9 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000580 Hom.: 0

Bravo AF: 0.00149

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	IRF5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.40
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs183734949; hg19: chr7-128582340;