NM_001098629.3:c.*555G>A

Variant names:

• chr7-128949373-G-A
• rs10954213
• NM_001098629.3:c.*555G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098629.3(IRF5):​c.*555G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,430 control chromosomes in the GnomAD database, including 25,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.58 (25754 hom., cov: 34)
  • Exomes 𝑓: 0.50 (28 hom.)
• Consequence: IRF5 NM_001098629.3 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.53
• Publications: 155 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF5	NM_001098629.3	MANE Select	c.*555G>A		3_prime_UTR	Exon 9 of 9	NP_001092099.1
	IRF5	NM_001347928.2		c.*555G>A		3_prime_UTR	Exon 9 of 9	NP_001334857.1
	IRF5	NM_001364314.2		c.*555G>A		3_prime_UTR	Exon 9 of 9	NP_001351243.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF5	ENST00000357234.10	TSL:1 MANE Select	c.*555G>A		3_prime_UTR	Exon 9 of 9	ENSP00000349770.5
	IRF5	ENST00000402030.6	TSL:1	c.*555G>A		3_prime_UTR	Exon 9 of 9	ENSP00000385352.2
	IRF5	ENST00000465603.5	TSL:5	n.*1580G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000418534.1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87999 AN: 152102 Hom.: 25745 Cov.: 34

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.500 AC: 105 AN: 210 Hom.: 28 Cov.: 0 AF XY: 0.510 AC XY: 52 AN XY: 102

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 7 AN: 14

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 3 AN: 6

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.505 AC: 92 AN: 182

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.578 AC: 88047 AN: 152220 Hom.: 25754 Cov.: 34 AF XY: 0.576 AC XY: 42895 AN XY: 74414

African (AFR) AF: 0.529 AC: 21980 AN: 41526

American (AMR) AF: 0.524 AC: 8020 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2499 AN: 3472

East Asian (EAS) AF: 0.475 AC: 2462 AN: 5182

South Asian (SAS) AF: 0.616 AC: 2972 AN: 4822

European-Finnish (FIN) AF: 0.620 AC: 6566 AN: 10586

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41531 AN: 68014

Other (OTH) AF: 0.595 AC: 1260 AN: 2116

Alfa AF: 0.590 Hom.: 18838

Bravo AF: 0.571

Asia WGS AF: 0.527 AC: 1834 AN: 3476

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Systemic lupus erythematosus, susceptibility to, 10 Other:1

Mar 15, 2008

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs10954213; hg19: chr7-128589427;