rs2070726

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002198.3(IRF1):​c.667+205G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 677,058 control chromosomes in the GnomAD database, including 41,450 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 0.38 ( 11245 hom., cov: 31)
Exomes 𝑓: 0.34 ( 30205 hom. )

Consequence

IRF1
NM_002198.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.420
Variant links:
Genes affected
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-AS1 (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IRF1NM_002198.3 linkuse as main transcriptc.667+205G>T intron_variant ENST00000245414.9 NP_002189.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IRF1ENST00000245414.9 linkuse as main transcriptc.667+205G>T intron_variant 1 NM_002198.3 ENSP00000245414 P1
IRF1-AS1ENST00000612967.2 linkuse as main transcriptn.281-146C>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.378
AC:
57360
AN:
151632
Hom.:
11231
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.486
Gnomad AMI
AF:
0.228
Gnomad AMR
AF:
0.342
Gnomad ASJ
AF:
0.323
Gnomad EAS
AF:
0.360
Gnomad SAS
AF:
0.408
Gnomad FIN
AF:
0.328
Gnomad MID
AF:
0.491
Gnomad NFE
AF:
0.333
Gnomad OTH
AF:
0.360
GnomAD4 exome
AF:
0.335
AC:
176235
AN:
525308
Hom.:
30205
Cov.:
6
AF XY:
0.337
AC XY:
93312
AN XY:
276848
show subpopulations
Gnomad4 AFR exome
AF:
0.487
Gnomad4 AMR exome
AF:
0.328
Gnomad4 ASJ exome
AF:
0.316
Gnomad4 EAS exome
AF:
0.325
Gnomad4 SAS exome
AF:
0.382
Gnomad4 FIN exome
AF:
0.327
Gnomad4 NFE exome
AF:
0.323
Gnomad4 OTH exome
AF:
0.345
GnomAD4 genome
AF:
0.378
AC:
57417
AN:
151750
Hom.:
11245
Cov.:
31
AF XY:
0.377
AC XY:
27991
AN XY:
74154
show subpopulations
Gnomad4 AFR
AF:
0.486
Gnomad4 AMR
AF:
0.342
Gnomad4 ASJ
AF:
0.323
Gnomad4 EAS
AF:
0.359
Gnomad4 SAS
AF:
0.409
Gnomad4 FIN
AF:
0.328
Gnomad4 NFE
AF:
0.333
Gnomad4 OTH
AF:
0.360
Alfa
AF:
0.203
Hom.:
386
Bravo
AF:
0.382
Asia WGS
AF:
0.377
AC:
1312
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
12
DANN
Benign
0.66

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2070726; hg19: chr5-131821738; COSMIC: COSV55376588; COSMIC: COSV55376588; API