rs3757385

Variant names:

• chr7-128937250-T-G
• rs3757385
• NM_001347928.2:c.-27T>G

Variant summary

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

The NM_001347928.2(IRF5):​c.-27T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,046 control chromosomes in the GnomAD database, including 25,853 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 (25853 hom., cov: 33)
• Consequence: IRF5 NM_001347928.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

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=-0.84).
• 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 rank	MANE	Protein	UniProt
IRF5	NM_001347928.2	c.-27T>G		5_prime_UTR_variant	Exon 1 of 9		NP_001334857.1
IRF5	XM_011516160.2	c.-596T>G		5_prime_UTR_variant	Exon 1 of 9		XP_011514462.1
IRF5	XM_047420338.1	c.-596T>G		5_prime_UTR_variant	Exon 1 of 9		XP_047276294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000652525.1	c.-456T>G		upstream_gene_variant				ENSP00000498293.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87631 AN: 151928 Hom.: 25835 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.577 AC: 87683 AN: 152046 Hom.: 25853 Cov.: 33 AF XY: 0.574 AC XY: 42693 AN XY: 74328

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.600

Alfa AF: 0.621 Hom.: 36541

Bravo AF: 0.564

Asia WGS AF: 0.477 AC: 1661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3757385; hg19: chr7-128577304;