rs3807135

Positions:

• chr7-128937563-T-C

Variant summary

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

The ENST00000652525.1(IRF5):​c.-143T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,132 control chromosomes in the GnomAD database, including 26,359 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 0.58 (26333 hom., cov: 33)
  • Exomes 𝑓: 0.63 (26 hom.)
• Consequence: IRF5 ENST00000652525.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	XM_011516160.2	c.-283T>C		5_prime_UTR_variant	1/9		XP_011514462.1
IRF5	XM_047420338.1	c.-283T>C		5_prime_UTR_variant	1/9		XP_047276294.1
IRF5	NM_001347928.2	c.-12+298T>C		intron_variant			NP_001334857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000652525.1	c.-143T>C		5_prime_UTR_variant	1/2			ENSP00000498293
IRF5	ENST00000489702.6			upstream_gene_variant		5		ENSP00000418037

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88510 AN: 151874 Hom.: 26318 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.607

GnomAD4 exome AF: 0.634 AC: 90 AN: 142 Hom.: 26 Cov.: 0 AF XY: 0.683 AC XY: 71 AN XY: 104

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.583 AC: 88562 AN: 151990 Hom.: 26333 Cov.: 33 AF XY: 0.580 AC XY: 43135 AN XY: 74316

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.602

Alfa AF: 0.604 Hom.: 8645

Bravo AF: 0.570

Asia WGS AF: 0.476 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3807135; hg19: chr7-128577617;