rs11770589

Variant names:

• chr7-128949434-G-A
• rs11770589
• NM_001098629.3:c.*616G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-128949434-G-A
• chr7-128949434-G-C
• chr7-128949434-G-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.*616G>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 0.468 in 152,122 control chromosomes in the GnomAD database, including 16,937 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 0.47 (16932 hom., cov: 33)
  • Exomes 𝑓: 0.40 (5 hom.)
• Consequence: IRF5 NM_001098629.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 29 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 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.*616G>A		3_prime_UTR	Exon 9 of 9	NP_001092099.1	Q13568-2
	IRF5	NM_001347928.2		c.*616G>A		3_prime_UTR	Exon 9 of 9	NP_001334857.1	Q13568-2
	IRF5	NM_001364314.2		c.*616G>A		3_prime_UTR	Exon 9 of 9	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.*616G>A		3_prime_UTR	Exon 9 of 9	ENSP00000349770.5	Q13568-2
	IRF5	ENST00000402030.6	TSL:1	c.*616G>A		3_prime_UTR	Exon 9 of 9	ENSP00000385352.2	Q13568-1
	IRF5	ENST00000489702.6	TSL:5	c.*616G>A		3_prime_UTR	Exon 9 of 9	ENSP00000418037.2	Q13568-2

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71186 AN: 151946 Hom.: 16921 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.400 AC: 24 AN: 60 Hom.: 5 Cov.: 0 AF XY: 0.385 AC XY: 10 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.333 AC: 2 AN: 6

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: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.400 AC: 20 AN: 50

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.468 AC: 71228 AN: 152062 Hom.: 16932 Cov.: 33 AF XY: 0.464 AC XY: 34502 AN XY: 74308

African (AFR) AF: 0.436 AC: 18086 AN: 41474

American (AMR) AF: 0.380 AC: 5805 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2101 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2456 AN: 5174

South Asian (SAS) AF: 0.463 AC: 2228 AN: 4816

European-Finnish (FIN) AF: 0.475 AC: 5014 AN: 10564

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33833 AN: 67958

Other (OTH) AF: 0.482 AC: 1018 AN: 2112

Alfa AF: 0.443 Hom.: 3554

Bravo AF: 0.461

Asia WGS AF: 0.464 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.34
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: rs11770589; hg19: chr7-128589488;