rs2236350

chr14-24161801-C-Achr14-24161801-C-G

Variant summary

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

The NM_006084.5(IRF9):c.-1-343C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 152,188 control chromosomes in the GnomAD database, including 864 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 0.087 (864 hom., cov: 32)
• Consequence: IRF9 NM_006084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357

Genes affected

IRF9 (HGNC:6131): (interferon regulatory factor 9) 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. Mutations in this gene result in Immunodeficiency 65. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF9	NM_006084.5	c.-1-343C>A		intron_variant		ENST00000396864.8
IRF9	NM_001385400.1	c.-1-343C>A		intron_variant
IRF9	NM_001385401.1	c.-1-343C>A		intron_variant
IRF9	NM_001385402.1	c.-1-343C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF9	ENST00000396864.8	c.-1-343C>A		intron_variant		1	NM_006084.5	P2

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13279 AN: 152070 Hom.: 869 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.0872 AC: 13278 AN: 152188 Hom.: 864 Cov.: 32 AF XY: 0.0911 AC XY: 6776 AN XY: 74398

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.0723

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.0535

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.0894

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0465 Hom.: 53

Bravo AF: 0.0817

Asia WGS AF: 0.158 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.5
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2236350; hg19: chr14-24631010;