rs2236350

Variant names:

• chr14-24161801-C-A
• rs2236350
• NM_006084.5:c.-1-343C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-24161801-C-A
• chr14-24161801-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

IRF9 Gene-Disease associations (from GenCC):

• immunodeficiency 65, susceptibility to viral infections

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000259529 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006084.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF9	NM_006084.5	MANE Select	c.-1-343C>A		intron	N/A	NP_006075.3
	IRF9	NM_001385400.1		c.-1-343C>A		intron	N/A	NP_001372329.1
	IRF9	NM_001385401.1		c.-1-343C>A		intron	N/A	NP_001372330.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF9	ENST00000396864.8	TSL:1 MANE Select	c.-1-343C>A		intron	N/A	ENSP00000380073.3
	ENSG00000259529	ENST00000558468.2	TSL:2	n.*766-343C>A		intron	N/A	ENSP00000457512.2
	IRF9	ENST00000559863.2	TSL:3	n.36C>A		non_coding_transcript_exon	Exon 1 of 6

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

African (AFR) AF: 0.0519 AC: 2156 AN: 41530

American (AMR) AF: 0.0723 AC: 1106 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3472

East Asian (EAS) AF: 0.350 AC: 1805 AN: 5162

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4818

European-Finnish (FIN) AF: 0.146 AC: 1542 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0894 AC: 6081 AN: 68006

Other (OTH) AF: 0.0818 AC: 173 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.60
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236350; hg19: chr14-24631010;