rs7657540

Positions:

• chr4-184442675-T-C
• chr4-184442675-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002199.4(IRF2):​c.-6-13605A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,658 control chromosomes in the GnomAD database, including 35,181 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 0.67 (35181 hom., cov: 28)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

Genes affected

IRF2 (HGNC:6117): (interferon regulatory factor 2) IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-6-13605A>G		intron_variant		ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.-6-13605A>G		intron_variant		1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102188 AN: 151540 Hom.: 35155 Cov.: 28

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.674 AC: 102253 AN: 151658 Hom.: 35181 Cov.: 28 AF XY: 0.673 AC XY: 49850 AN XY: 74080

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.660

Alfa AF: 0.755 Hom.: 38371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.24

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: rs7657540; hg19: chr4-185363829;