rs2549007

Variant names:

• chr5-132491183-T-C
• rs2549007
• ENST00000638452.2:c.-169+41494T>C

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-169+41494T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,628 control chromosomes in the GnomAD database, including 28,383 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 (28383 hom., cov: 34)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 10 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 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+41494T>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91658 AN: 151510 Hom.: 28364 Cov.: 34

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.605 AC: 91720 AN: 151628 Hom.: 28383 Cov.: 34 AF XY: 0.607 AC XY: 44937 AN XY: 74066

African (AFR) AF: 0.460 AC: 19010 AN: 41364

American (AMR) AF: 0.651 AC: 9942 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2346 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3272 AN: 5138

South Asian (SAS) AF: 0.589 AC: 2834 AN: 4810

European-Finnish (FIN) AF: 0.668 AC: 7021 AN: 10504

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45127 AN: 67764

Other (OTH) AF: 0.629 AC: 1325 AN: 2108

Alfa AF: 0.627 Hom.: 3743

Bravo AF: 0.600

Asia WGS AF: 0.619 AC: 2149 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.69
PhyloP100		-0.41
PromoterAI		0.26	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2549007; hg19: chr5-131826875; COSMIC: COSV55376700; COSMIC: COSV55376700;