rs736801

Variant names:

• chr5-132497907-C-T
• rs736801
• ENST00000638452.2:c.-169+48218C>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+48218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,104 control chromosomes in the GnomAD database, including 6,155 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 0.25 (6155 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 19 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=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 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+48218C>T		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38369 AN: 151986 Hom.: 6153 Cov.: 32

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.252 AC: 38379 AN: 152104 Hom.: 6155 Cov.: 32 AF XY: 0.242 AC XY: 17986 AN XY: 74384

African (AFR) AF: 0.0907 AC: 3765 AN: 41506

American (AMR) AF: 0.277 AC: 4226 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1152 AN: 3472

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5178

South Asian (SAS) AF: 0.100 AC: 482 AN: 4818

European-Finnish (FIN) AF: 0.256 AC: 2715 AN: 10592

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24736 AN: 67940

Other (OTH) AF: 0.308 AC: 652 AN: 2114

Alfa AF: 0.224 Hom.: 1360

Bravo AF: 0.252

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.71
PhyloP100		0.40

Splicing

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

Other links and lift over

dbSNP: rs736801; hg19: chr5-131833599; COSMIC: COSV60199099;