Genetic Variant IRF9:p.Thr36Thr (chr14-24162252-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.464

Variant links:

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 links:

ENSG00000259529 (HGNC:):

ENSG00000259529 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF9	NM_006084.5 link	c.108C>T	p.Thr36Thr	synonymous_variant	Exon 2 of 9	ENST00000396864.8	NP_006075.3	Q00978
IRF9	NM_001385400.1 link	c.108C>T	p.Thr36Thr	synonymous_variant	Exon 2 of 10		NP_001372329.1
IRF9	NM_001385401.1 link	c.108C>T	p.Thr36Thr	synonymous_variant	Exon 2 of 9		NP_001372330.1
IRF9	NM_001385402.1 link	c.108C>T	p.Thr36Thr	synonymous_variant	Exon 2 of 9		NP_001372331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IRF9	ENST00000396864.8 link	c.108C>T	p.Thr36Thr	synonymous_variant	Exon 2 of 9	1	NM_006084.5	ENSP00000380073.3	Q00978
ENSG00000259529	ENST00000558468.2 link	n.*874C>T		non_coding_transcript_exon_variant	Exon 22 of 29	2		ENSP00000457512.2	A0A0B4J293
ENSG00000259529	ENST00000558468.2 link	n.*874C>T		3_prime_UTR_variant	Exon 22 of 29	2		ENSP00000457512.2	A0A0B4J293

Frequencies

GnomAD3 genomes

AF:

0.0167

AC:

2540

AN:

152138

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00425

AC:

1069

AN:

251406

Hom.:

AF XY:

0.00291

AC XY:

395

AN XY:

135862

show subpopulations

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 SAS 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.:

Cov.:

AF XY:

0.00128

AC XY:

929

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0560

Gnomad4 AMR exome

AF:

0.00349

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.0167

AC:

2544

AN:

152256

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1217

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0578

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00805

Hom.:

Bravo

AF:

0.0192

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over