rs10139346

Variant names:

• chr14-24162252-C-T
• rs10139346
• NM_006084.5:c.108C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006084.5(IRF9):​c.108C>T​(p.Thr36Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,614,146 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (74 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (53 hom.)
• Consequence: IRF9 NM_006084.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.464
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 14-24162252-C-T is Benign according to our data. Variant chr14-24162252-C-T is described in ClinVar as Benign. ClinVar VariationId is 787110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.464 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0558 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF9	NM_006084.5	MANE Select	c.108C>T	p.Thr36Thr	synonymous	Exon 2 of 9	NP_006075.3
	IRF9	NM_001385400.1		c.108C>T	p.Thr36Thr	synonymous	Exon 2 of 10	NP_001372329.1	A0A8V8TMJ8
	IRF9	NM_001385401.1		c.108C>T	p.Thr36Thr	synonymous	Exon 2 of 9	NP_001372330.1	H0YNP4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF9	ENST00000396864.8	TSL:1 MANE Select	c.108C>T	p.Thr36Thr	synonymous	Exon 2 of 9	ENSP00000380073.3	Q00978
	ENSG00000259529	ENST00000558468.2	TSL:2	n.*874C>T		non_coding_transcript_exon	Exon 22 of 29	ENSP00000457512.2
	ENSG00000259529	ENST00000558468.2	TSL:2	n.*874C>T		3_prime_UTR	Exon 22 of 29	ENSP00000457512.2

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2540 AN: 152138 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00425 AC: 1069 AN: 251406 AF XY: 0.00291

Gnomad AFR exome AF: 0.0580

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00155 AC: 2272 AN: 1461890 Hom.: 53 Cov.: 31 AF XY: 0.00128 AC XY: 929 AN XY: 727248

African (AFR) AF: 0.0560 AC: 1874 AN: 33478

American (AMR) AF: 0.00349 AC: 156 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1112010

Other (OTH) AF: 0.00313 AC: 189 AN: 60396

GnomAD4 genome AF: 0.0167 AC: 2544 AN: 152256 Hom.: 74 Cov.: 32 AF XY: 0.0163 AC XY: 1217 AN XY: 74452

African (AFR) AF: 0.0578 AC: 2398 AN: 41520

American (AMR) AF: 0.00758 AC: 116 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00800 Hom.: 34

Bravo AF: 0.0192

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs10139346; hg19: chr14-24631461;