Genetic Variant ENST00000640655:c.-388T>C (chr5-132486441-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The ENST00000640655(ENSG00000283782):c.-388T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,608,276 control chromosomes in the GnomAD database, including 97,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11331 hom., cov: 33)

Exomes 𝑓: 0.34 ( 85866 hom. )

Consequence

ENSG00000283782
ENST00000640655 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

ENSG00000283782 (HGNC:):

ENSG00000283782 links:

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-132486441-T-C is Benign according to our data. Variant chr5-132486441-T-C is described in ClinVar as [Benign]. Clinvar id is 2688382.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 rank	MANE	Protein	UniProt
IRF1	NM_002198.3 link	c.545-68A>G		intron_variant	Intron 6 of 9	ENST00000245414.9	NP_002189.1	P10914Q6FHN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000640655 link	c.-388T>C		5_prime_UTR_variant	Exon 2 of 26	5		ENSP00000491596.2		A0A1W2PQ90
IRF1	ENST00000245414.9 link	c.545-68A>G		intron_variant	Intron 6 of 9	1	NM_002198.3	ENSP00000245414.4		P10914

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57648

AN:

152030

Hom.:

11317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.229

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:

0.490

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.360

GnomAD3 exomes

AF:

0.347

AC:

85735

AN:

246886

Hom.:

14978

AF XY:

0.347

AC XY:

46390

AN XY:

133812

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:

0.322

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.341

AC:

496764

AN:

1456128

Hom.:

85866

Cov.:

AF XY:

0.342

AC XY:

247669

AN XY:

724490

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:

0.325

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.379

AC:

57705

AN:

152148

Hom.:

11331

Cov.:

AF XY:

0.378

AC XY:

28154

AN XY:

74388

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.:

2051

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.88

CADD

Benign

1.1

DANN

Benign

0.42

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