chr7-128949373-G-A

Position:

• chr7-128949373-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098629.3(IRF5):​c.*555G>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 0.578 in 152,430 control chromosomes in the GnomAD database, including 25,782 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 0.58 (25754 hom., cov: 34)
  • Exomes 𝑓: 0.50 (28 hom.)
• Consequence: IRF5 NM_001098629.3 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.53

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.*555G>A		3_prime_UTR_variant	9/9	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.*555G>A		3_prime_UTR_variant	9/9	1	NM_001098629.3	ENSP00000349770

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87999 AN: 152102 Hom.: 25745 Cov.: 34

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.500 AC: 105 AN: 210 Hom.: 28 Cov.: 0 AF XY: 0.510 AC XY: 52 AN XY: 102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.578 AC: 88047 AN: 152220 Hom.: 25754 Cov.: 34 AF XY: 0.576 AC XY: 42895 AN XY: 74414

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.595

Alfa AF: 0.599 Hom.: 10738

Bravo AF: 0.571

Asia WGS AF: 0.527 AC: 1834 AN: 3476

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Systemic lupus erythematosus, susceptibility to, 10 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 15, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs10954213; hg19: chr7-128589427;