7-128945050-A-G

Position:

• chr7-128945050-A-G

Variant summary

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

The NM_001098629.3(IRF5):​c.196-795A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,094 control chromosomes in the GnomAD database, including 12,064 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 0.40 (12064 hom., cov: 32)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.196-795A>G		intron_variant		ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.196-795A>G		intron_variant		1	NM_001098629.3	ENSP00000349770

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60022 AN: 151976 Hom.: 12049 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.395 AC: 60082 AN: 152094 Hom.: 12064 Cov.: 32 AF XY: 0.389 AC XY: 28902 AN XY: 74368

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.400

Alfa AF: 0.390 Hom.: 20248

Bravo AF: 0.398

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.28

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: rs1874328; hg19: chr7-128585104;