Variant 5-132486363-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002198.3(IRF1):c.555A>G(p.Pro185Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,611,130 control chromosomes in the GnomAD database, including 97,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11290 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86115 hom. )

Consequence

IRF1
NM_002198.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.11

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 links:

ENSG00000283782 (HGNC:):

ENSG00000283782 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 5-132486363-T-C is Benign according to our data. Variant chr5-132486363-T-C is described in ClinVar as [Benign]. Clinvar id is 2688380.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.11 with no splicing effect.

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
IRF1	NM_002198.3 linkuse as main transcript	c.555A>G	p.Pro185Pro	synonymous_variant	7/10	ENST00000245414.9	NP_002189.1	P10914Q6FHN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9 linkuse as main transcript	c.555A>G	p.Pro185Pro	synonymous_variant	7/10	1	NM_002198.3	ENSP00000245414.4		P10914
ENSG00000283782	ENST00000640655 linkuse as main transcript	c.-466T>C		5_prime_UTR_variant	2/26	5		ENSP00000491596.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57543

AN:

151918

Hom.:

11276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.360

GnomAD3 exomes

AF:

0.348

AC:

86806

AN:

249370

Hom.:

15316

AF XY:

0.348

AC XY:

46925

AN XY:

135010

show subpopulations

Gnomad AFR exome

AF:

0.486

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.345

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.357

GnomAD4 exome

AF:

0.341

AC:

497978

AN:

1459094

Hom.:

86115

Cov.:

AF XY:

0.342

AC XY:

248267

AN XY:

725888

show subpopulations

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.331

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.327

Gnomad4 NFE exome

AF:

0.335

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.379

AC:

57600

AN:

152036

Hom.:

11290

Cov.:

AF XY:

0.378

AC XY:

28098

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.487

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.360

Gnomad4 SAS

AF:

0.409

Gnomad4 FIN

AF:

0.329

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.360

Alfa

AF:

0.345

Hom.:

2356

Bravo

AF:

0.382

Asia WGS

AF:

0.377

AC:

1311

AN:

3478

EpiCase

AF:

0.329

EpiControl

AF:

0.325

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 submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 66% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.066

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over