rs2549002

Variant names:

• chr5-132493886-C-A
• rs2549002
• ENST00000638452.2:c.-169+44197C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132493886-C-A
• chr5-132493886-C-G
• chr5-132493886-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638452.2(ENSG00000283782):​c.-169+44197C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,956 control chromosomes in the GnomAD database, including 28,376 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 0.60 (28376 hom., cov: 31)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 14 publications found

Genes affected

ENSG00000283782 (HGNC:):

IRF1 (HGNC:6116): (interferon regulatory factor 1) The protein encoded by this gene is a transcriptional regulator and tumor suppressor, serving as an activator of genes involved in both innate and acquired immune responses. The encoded protein activates the transcription of genes involved in the body's response to viruses and bacteria, playing a role in cell proliferation, apoptosis, the immune response, and DNA damage response. This protein represses the transcription of several other genes. As a tumor suppressor, it both suppresses tumor cell growth and stimulates an immune response against tumor cells. Defects in this gene have been associated with gastric cancer, myelogenous leukemia, and lung cancer. [provided by RefSeq, Aug 2017]

IRF1 Gene-Disease associations (from GenCC):

• immunodeficiency 117

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000638452.2	c.-169+44197C>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91650 AN: 151838 Hom.: 28362 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.603 AC: 91701 AN: 151956 Hom.: 28376 Cov.: 31 AF XY: 0.605 AC XY: 44970 AN XY: 74270

African (AFR) AF: 0.452 AC: 18720 AN: 41434

American (AMR) AF: 0.651 AC: 9947 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2318 AN: 3466

East Asian (EAS) AF: 0.642 AC: 3320 AN: 5168

South Asian (SAS) AF: 0.592 AC: 2845 AN: 4808

European-Finnish (FIN) AF: 0.672 AC: 7094 AN: 10556

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.667 AC: 45283 AN: 67926

Other (OTH) AF: 0.628 AC: 1324 AN: 2108

Alfa AF: 0.499 Hom.: 1866

Bravo AF: 0.597

Asia WGS AF: 0.620 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.12
DANN	Benign	0.71
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2549002; hg19: chr5-131829578; COSMIC: COSV55376739; COSMIC: COSV55376739;