chr5-132486174-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002198.3(IRF1):​c.667+77A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,569,128 control chromosomes in the GnomAD database, including 94,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11295 hom., cov: 31)
Exomes 𝑓: 0.34 ( 83517 hom. )

Consequence

IRF1
NM_002198.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0520
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 5-132486174-T-G is Benign according to our data. Variant chr5-132486174-T-G is described in ClinVar as [Benign]. Clinvar id is 2688385.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 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+77A>C 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+77A>C intron_variant 1 NM_002198.3 ENSP00000245414 P1
IRF1-AS1ENST00000612967.2 linkuse as main transcriptn.281-18T>G intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.379
AC:
57516
AN:
151704
Hom.:
11281
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.487
Gnomad AMI
AF:
0.226
Gnomad AMR
AF:
0.343
Gnomad ASJ
AF:
0.323
Gnomad EAS
AF:
0.362
Gnomad SAS
AF:
0.409
Gnomad FIN
AF:
0.330
Gnomad MID
AF:
0.491
Gnomad NFE
AF:
0.333
Gnomad OTH
AF:
0.360
GnomAD3 exomes
AF:
0.348
AC:
83187
AN:
239334
Hom.:
14719
AF XY:
0.347
AC XY:
45029
AN XY:
129806
show subpopulations
Gnomad AFR exome
AF:
0.488
Gnomad AMR exome
AF:
0.326
Gnomad ASJ exome
AF:
0.313
Gnomad EAS exome
AF:
0.345
Gnomad SAS exome
AF:
0.389
Gnomad FIN exome
AF:
0.324
Gnomad NFE exome
AF:
0.330
Gnomad OTH exome
AF:
0.354
GnomAD4 exome
AF:
0.341
AC:
482912
AN:
1417306
Hom.:
83517
Cov.:
25
AF XY:
0.342
AC XY:
240278
AN XY:
703456
show subpopulations
Gnomad4 AFR exome
AF:
0.491
Gnomad4 AMR exome
AF:
0.330
Gnomad4 ASJ exome
AF:
0.314
Gnomad4 EAS exome
AF:
0.330
Gnomad4 SAS exome
AF:
0.386
Gnomad4 FIN exome
AF:
0.328
Gnomad4 NFE exome
AF:
0.334
Gnomad4 OTH exome
AF:
0.348
GnomAD4 genome
AF:
0.379
AC:
57573
AN:
151822
Hom.:
11295
Cov.:
31
AF XY:
0.378
AC XY:
28073
AN XY:
74186
show subpopulations
Gnomad4 AFR
AF:
0.487
Gnomad4 AMR
AF:
0.343
Gnomad4 ASJ
AF:
0.323
Gnomad4 EAS
AF:
0.361
Gnomad4 SAS
AF:
0.410
Gnomad4 FIN
AF:
0.330
Gnomad4 NFE
AF:
0.333
Gnomad4 OTH
AF:
0.360
Alfa
AF:
0.349
Hom.:
2088
Bravo
AF:
0.382
Asia WGS
AF:
0.377
AC:
1312
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This variant is classified as Benign based on local population frequency. This variant was detected in 65% of patients studied by a panel of primary immunodeficiencies. Number of patients: 57. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
7.0
DANN
Benign
0.63
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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: rs10214312; hg19: chr5-131821866; COSMIC: COSV55376764; COSMIC: COSV55376764; API