7-128940626-G-T

Variant names:

• chr7-128940626-G-T
• rs3807306
• NM_001098629.3:c.-11-1445G>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.-11-1445G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 153,516 control chromosomes in the GnomAD database, including 14,830 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 0.43 (14684 hom., cov: 34)
  • Exomes 𝑓: 0.46 (146 hom.)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 124 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 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.-11-1445G>T		intron	N/A	NP_001092099.1	Q13568-2
	IRF5	NM_001347928.2		c.-11-1445G>T		intron	N/A	NP_001334857.1	Q13568-2
	IRF5	NM_001098630.3		c.-11-1445G>T		intron	N/A	NP_001092100.1	Q13568-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF5	ENST00000357234.10	TSL:1 MANE Select	c.-11-1445G>T		intron	N/A	ENSP00000349770.5	Q13568-2
	IRF5	ENST00000402030.6	TSL:1	c.-11-1445G>T		intron	N/A	ENSP00000385352.2	Q13568-1
	IRF5	ENST00000477535.5	TSL:1	c.-11-1445G>T		intron	N/A	ENSP00000419950.1	Q13568-5

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65234 AN: 152036 Hom.: 14681 Cov.: 34

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.456 AC: 624 AN: 1368 Hom.: 146 Cov.: 0 AF XY: 0.453 AC XY: 338 AN XY: 746

African (AFR) AF: 0.294 AC: 10 AN: 34

American (AMR) AF: 0.556 AC: 10 AN: 18

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 15 AN: 34

East Asian (EAS) AF: 0.171 AC: 24 AN: 140

South Asian (SAS) AF: 0.333 AC: 4 AN: 12

European-Finnish (FIN) AF: 0.508 AC: 64 AN: 126

Middle Eastern (MID) AF: 0.583 AC: 7 AN: 12

European-Non Finnish (NFE) AF: 0.488 AC: 443 AN: 908

Other (OTH) AF: 0.560 AC: 47 AN: 84

GnomAD4 genome AF: 0.429 AC: 65252 AN: 152148 Hom.: 14684 Cov.: 34 AF XY: 0.425 AC XY: 31572 AN XY: 74372

African (AFR) AF: 0.331 AC: 13718 AN: 41506

American (AMR) AF: 0.421 AC: 6443 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2059 AN: 3472

East Asian (EAS) AF: 0.188 AC: 977 AN: 5190

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4818

European-Finnish (FIN) AF: 0.490 AC: 5186 AN: 10580

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.488 AC: 33175 AN: 67968

Other (OTH) AF: 0.462 AC: 977 AN: 2114

Alfa AF: 0.459 Hom.: 41360

Bravo AF: 0.421

Asia WGS AF: 0.294 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.49
PhyloP100		-0.41
PromoterAI		0.0044	Neutral
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: rs3807306; hg19: chr7-128580680;