Variant 5-132486973-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002198.3(IRF1):c.345C>G(p.Leu115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,614,166 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 14 hom., cov: 32)

Exomes 𝑓: 0.013 ( 171 hom. )

Consequence

IRF1
NM_002198.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.443

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:

IRF1-AS1 (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

IRF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 5-132486973-G-C is Benign according to our data. Variant chr5-132486973-G-C is described in ClinVar as [Benign]. Clinvar id is 790794.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.443 with no splicing effect.

BS2

High AC in GnomAd at 1252 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF1	NM_002198.3 linkuse as main transcript	c.345C>G	p.Leu115=	synonymous_variant	4/10	ENST00000245414.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF1	ENST00000245414.9 linkuse as main transcript	c.345C>G	p.Leu115=	synonymous_variant	4/10	1	NM_002198.3	P1
IRF1-AS1	ENST00000612967.2 linkuse as main transcript	n.1062G>C		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes

AF:

0.00823

AC:

1252

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00865

AC:

2175

AN:

251434

Hom.:

AF XY:

0.00891

AC XY:

1211

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00335

Gnomad ASJ exome

AF:

0.00605

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00768

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.00831

GnomAD4 exome

AF:

0.0130

AC:

19049

AN:

1461844

Hom.:

171

Cov.:

AF XY:

0.0128

AC XY:

9278

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00736

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.0125

GnomAD4 genome

AF:

0.00822

AC:

1252

AN:

152322

Hom.:

Cov.:

AF XY:

0.00799

AC XY:

595

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00714

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0125

EpiControl

AF:

0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Benign

0.77

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