7-128949434-G-A

Position:

• chr7-128949434-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.*616G>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 0.468 in 152,122 control chromosomes in the GnomAD database, including 16,937 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 0.47 (16932 hom., cov: 33)
  • Exomes 𝑓: 0.40 (5 hom.)
• Consequence: IRF5 NM_001098629.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342

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 = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF5	NM_001098629.3	c.*616G>A		3_prime_UTR_variant	9/9	ENST00000357234.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF5	ENST00000357234.10	c.*616G>A		3_prime_UTR_variant	9/9	1	NM_001098629.3

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71186 AN: 151946 Hom.: 16921 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.400 AC: 24 AN: 60 Hom.: 5 Cov.: 0 AF XY: 0.385 AC XY: 10 AN XY: 26

Gnomad4 AMR exome AF: 0.333

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.400

GnomAD4 genome AF: 0.468 AC: 71228 AN: 152062 Hom.: 16932 Cov.: 33 AF XY: 0.464 AC XY: 34502 AN XY: 74308

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.482

Alfa AF: 0.443 Hom.: 3014

Bravo AF: 0.461

Asia WGS AF: 0.464 AC: 1614 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	1.6
DANN	Benign	0.66

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: rs11770589; hg19: chr7-128589488;