rs10954214

Variant names:

• chr7-128949579-C-T
• rs10954214
• NM_001098629.3:c.*761C>T

Variant summary

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

The NM_001098629.3(IRF5):​c.*761C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,924 control chromosomes in the GnomAD database, including 31,083 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 0.64 (31076 hom., cov: 31)
  • Exomes 𝑓: 0.66 (7 hom.)
• Consequence: IRF5 NM_001098629.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665
• Publications: 17 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=-0.48).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 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.*761C>T		3_prime_UTR	Exon 9 of 9	NP_001092099.1
	IRF5	NM_001347928.2		c.*761C>T		3_prime_UTR	Exon 9 of 9	NP_001334857.1
	IRF5	NM_001364314.2		c.*761C>T		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.*761C>T		3_prime_UTR	Exon 9 of 9	ENSP00000349770.5
	IRF5	ENST00000402030.6	TSL:1	c.*761C>T		3_prime_UTR	Exon 9 of 9	ENSP00000385352.2
	IRF5	ENST00000700148.1		n.2542C>T		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96577 AN: 151774 Hom.: 31050 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 0.656 AC: 21 AN: 32 Hom.: 7 Cov.: 0 AF XY: 0.750 AC XY: 9 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.625 AC: 15 AN: 24

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.636 AC: 96647 AN: 151892 Hom.: 31076 Cov.: 31 AF XY: 0.637 AC XY: 47302 AN XY: 74214

African (AFR) AF: 0.593 AC: 24557 AN: 41400

American (AMR) AF: 0.563 AC: 8604 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2621 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2872 AN: 5144

South Asian (SAS) AF: 0.690 AC: 3320 AN: 4814

European-Finnish (FIN) AF: 0.734 AC: 7734 AN: 10538

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44760 AN: 67938

Other (OTH) AF: 0.646 AC: 1363 AN: 2110

Alfa AF: 0.633 Hom.: 6291

Bravo AF: 0.623

Asia WGS AF: 0.629 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.67
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: rs10954214; hg19: chr7-128589633;