rs2292383

Variant names:

• chr6-402087-T-C
• rs2292383
• NM_002460.4:c.1099+310T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002460.4(IRF4):​c.1099+310T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 152,236 control chromosomes in the GnomAD database, including 559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.078 (559 hom., cov: 33)
• Consequence: IRF4 NM_002460.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.342
• Publications: 10 publications found

Genes affected

IRF4 (HGNC:6119): (interferon regulatory factor 4) The protein encoded by this gene belongs to the IRF (interferon regulatory factor) family of transcription factors, characterized by an unique tryptophan pentad repeat DNA-binding domain. The IRFs are important in the regulation of interferons in response to infection by virus, and in the regulation of interferon-inducible genes. This family member is lymphocyte specific and negatively regulates Toll-like-receptor (TLR) signaling that is central to the activation of innate and adaptive immune systems. A chromosomal translocation involving this gene and the IgH locus, t(6;14)(p25;q32), may be a cause of multiple myeloma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-402087-T-C is Benign according to our data. Variant chr6-402087-T-C is described in ClinVar as [Benign]. Clinvar id is 1263574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF4	NM_002460.4	c.1099+310T>C		intron_variant	Intron 7 of 8	ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9	c.1099+310T>C		intron_variant	Intron 7 of 8	1	NM_002460.4	ENSP00000370343.4
IRF4	ENST00000696871.1	c.1096+310T>C		intron_variant	Intron 7 of 8			ENSP00000512940.1
IRF4	ENST00000493114.2	n.1096+310T>C		intron_variant	Intron 7 of 9	5		ENSP00000436094.2

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11877 AN: 152118 Hom.: 556 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0495

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.0781 AC: 11897 AN: 152236 Hom.: 559 Cov.: 33 AF XY: 0.0760 AC XY: 5660 AN XY: 74442

African (AFR) AF: 0.121 AC: 5038 AN: 41532

American (AMR) AF: 0.0620 AC: 948 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3470

East Asian (EAS) AF: 0.0265 AC: 137 AN: 5168

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4824

European-Finnish (FIN) AF: 0.0495 AC: 525 AN: 10610

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0654 AC: 4448 AN: 68016

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0688 Hom.: 162

Bravo AF: 0.0822

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2021

GeneDx

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	-0.83
CADD	Benign	1.5
DANN	Benign	0.29
PhyloP100		-0.34
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: rs2292383; hg19: chr6-402087;