NM_001098629.3:c.*128T>C

Variant names:

• chr7-128948946-T-C
• rs2070197
• NM_001098629.3:c.*128T>C

Variant summary

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

The NM_001098629.3(IRF5):​c.*128T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,201,678 control chromosomes in the GnomAD database, including 8,087 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 0.090 (862 hom., cov: 33)
  • Exomes 𝑓: 0.11 (7225 hom.)
• Consequence: IRF5 NM_001098629.3 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.862
• Publications: 78 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF5	NM_001098629.3	MANE Select	c.*128T>C		3_prime_UTR	Exon 9 of 9	NP_001092099.1
	IRF5	NM_001347928.2		c.*128T>C		3_prime_UTR	Exon 9 of 9	NP_001334857.1
	IRF5	NM_001364314.2		c.*128T>C		3_prime_UTR	Exon 9 of 9	NP_001351243.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF5	ENST00000357234.10	TSL:1 MANE Select	c.*128T>C		3_prime_UTR	Exon 9 of 9	ENSP00000349770.5
	IRF5	ENST00000402030.6	TSL:1	c.*128T>C		3_prime_UTR	Exon 9 of 9	ENSP00000385352.2
	IRF5	ENST00000489702.6	TSL:5	c.*128T>C		3_prime_UTR	Exon 9 of 9	ENSP00000418037.2

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13755 AN: 152100 Hom.: 865 Cov.: 33

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.110 AC: 115067 AN: 1049460 Hom.: 7225 Cov.: 14 AF XY: 0.111 AC XY: 57904 AN XY: 522450

African (AFR) AF: 0.0189 AC: 456 AN: 24162

American (AMR) AF: 0.191 AC: 4546 AN: 23764

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2008 AN: 17842

East Asian (EAS) AF: 0.000253 AC: 9 AN: 35524

South Asian (SAS) AF: 0.157 AC: 9560 AN: 60908

European-Finnish (FIN) AF: 0.152 AC: 4881 AN: 32194

Middle Eastern (MID) AF: 0.123 AC: 384 AN: 3128

European-Non Finnish (NFE) AF: 0.109 AC: 88236 AN: 805970

Other (OTH) AF: 0.108 AC: 4987 AN: 45968

GnomAD4 genome AF: 0.0903 AC: 13749 AN: 152218 Hom.: 862 Cov.: 33 AF XY: 0.0930 AC XY: 6922 AN XY: 74438

African (AFR) AF: 0.0243 AC: 1009 AN: 41556

American (AMR) AF: 0.139 AC: 2119 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5178

South Asian (SAS) AF: 0.154 AC: 741 AN: 4826

European-Finnish (FIN) AF: 0.145 AC: 1540 AN: 10610

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7649 AN: 67964

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.0983 Hom.: 138

Bravo AF: 0.0870

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	SYSTEMIC LUPUS ERYTHEMATOSUS, ASSOCIATION WITH SUSCEPTIBILITY TO, 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.40
PhyloP100		-0.86
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: rs2070197; hg19: chr7-128589000; COSMIC: COSV50857256; COSMIC: COSV50857256;