rs3778751

Variant names:

• chr7-128939994-A-T
• rs3778751
• NM_001098629.3:c.-12+1945A>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.-12+1945A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,490 control chromosomes in the GnomAD database, including 13,378 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 0.41 (13378 hom., cov: 32)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-12+1945A>T		intron_variant	Intron 1 of 8	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.-12+1945A>T		intron_variant	Intron 1 of 8	1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62637 AN: 151370 Hom.: 13374 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.463

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.414 AC: 62666 AN: 151490 Hom.: 13378 Cov.: 32 AF XY: 0.408 AC XY: 30197 AN XY: 74038

African (AFR) AF: 0.344 AC: 14244 AN: 41376

American (AMR) AF: 0.415 AC: 6331 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 1997 AN: 3448

East Asian (EAS) AF: 0.188 AC: 969 AN: 5146

South Asian (SAS) AF: 0.432 AC: 2078 AN: 4810

European-Finnish (FIN) AF: 0.415 AC: 4373 AN: 10528

Middle Eastern (MID) AF: 0.510 AC: 147 AN: 288

European-Non Finnish (NFE) AF: 0.460 AC: 31151 AN: 67662

Other (OTH) AF: 0.460 AC: 966 AN: 2100

Alfa AF: 0.434 Hom.: 1800

Bravo AF: 0.413

Asia WGS AF: 0.298 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.80
PhyloP100		0.48
PromoterAI		0.060	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: rs3778751; hg19: chr7-128580048;