rs10954214

chr7-128949579-C-T

Variant summary

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

The NM_001098629.3(IRF5):c.*761C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,924 control chromosomes in the GnomAD database, including 31,083 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 0.64 (31076 hom., cov: 31)
  • Exomes 𝑓: 0.66 (7 hom.)
• Consequence: IRF5 NM_001098629.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665

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=-0.48).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF5	NM_001098629.3	c.*761C>T		3_prime_UTR_variant	9/9	ENST00000357234.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF5	ENST00000357234.10	c.*761C>T		3_prime_UTR_variant	9/9	1	NM_001098629.3

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96577 AN: 151774 Hom.: 31050 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 0.656 AC: 21 AN: 32 Hom.: 7 Cov.: 0 AF XY: 0.750 AC XY: 9 AN XY: 12

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.636 AC: 96647 AN: 151892 Hom.: 31076 Cov.: 31 AF XY: 0.637 AC XY: 47302 AN XY: 74214

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.646

Alfa AF: 0.638 Hom.: 5451

Bravo AF: 0.623

Asia WGS AF: 0.629 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	13
Dann	Benign	0.71

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: rs10954214; hg19: chr7-128589633;