14-24162231-C-T

Variant names:

• chr14-24162231-C-T
• rs145197850
• NM_006084.5:c.87C>T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_006084.5(IRF9):​c.87C>T​(p.Cys29Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,614,118 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (25 hom.)
• Consequence: IRF9 NM_006084.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.352

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]

ENSG00000259529 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 14-24162231-C-T is Benign according to our data. Variant chr14-24162231-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 781705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.352 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF9	NM_006084.5	c.87C>T	p.Cys29Cys	synonymous_variant	Exon 2 of 9	ENST00000396864.8	NP_006075.3
IRF9	NM_001385400.1	c.87C>T	p.Cys29Cys	synonymous_variant	Exon 2 of 10		NP_001372329.1
IRF9	NM_001385401.1	c.87C>T	p.Cys29Cys	synonymous_variant	Exon 2 of 9		NP_001372330.1
IRF9	NM_001385402.1	c.87C>T	p.Cys29Cys	synonymous_variant	Exon 2 of 9		NP_001372331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF9	ENST00000396864.8	c.87C>T	p.Cys29Cys	synonymous_variant	Exon 2 of 9	1	NM_006084.5	ENSP00000380073.3
ENSG00000259529	ENST00000558468.2	n.*853C>T		non_coding_transcript_exon_variant	Exon 22 of 29	2		ENSP00000457512.2
ENSG00000259529	ENST00000558468.2	n.*853C>T		3_prime_UTR_variant	Exon 22 of 29	2		ENSP00000457512.2

Frequencies

GnomAD3 genomes AF: 0.00358 AC: 545 AN: 152116 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00579

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00330 AC: 830 AN: 251464 Hom.: 1 AF XY: 0.00315 AC XY: 428 AN XY: 135906

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.00327

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00388

Gnomad NFE exome AF: 0.00526

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00518 AC: 7579 AN: 1461884 Hom.: 25 Cov.: 31 AF XY: 0.00500 AC XY: 3639 AN XY: 727246

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00364

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00395

Gnomad4 NFE exome AF: 0.00618

Gnomad4 OTH exome AF: 0.00475

GnomAD4 genome AF: 0.00358 AC: 545 AN: 152234 Hom.: 1 Cov.: 32 AF XY: 0.00340 AC XY: 253 AN XY: 74430

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00321

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00434

Gnomad4 NFE AF: 0.00579

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00434 Hom.: 0

Bravo AF: 0.00315

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00458

EpiControl AF: 0.00492

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IRF9: BP4 -

IRF9-related disorder Benign:1

Oct 05, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.89

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: rs145197850; hg19: chr14-24631440;