Variant 1-1013490-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000624697.4(ISG15):c.-21-494C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 1,447,158 control chromosomes in the GnomAD database, including 652,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 62121 hom., cov: 34)

Exomes 𝑓: 0.95 ( 590006 hom. )

Consequence

ISG15
ENST00000624697.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.01

Variant links:

Genes affected

ISG15 (HGNC:4053): (ISG15 ubiquitin like modifier) The protein encoded by this gene is a ubiquitin-like protein that is conjugated to intracellular target proteins upon activation by interferon-alpha and interferon-beta. Several functions have been ascribed to the encoded protein, including chemotactic activity towards neutrophils, direction of ligated target proteins to intermediate filaments, cell-to-cell signaling, and antiviral activity during viral infections. While conjugates of this protein have been found to be noncovalently attached to intermediate filaments, this protein is sometimes secreted. [provided by RefSeq, Dec 2012]

ISG15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 1-1013490-C-G is Benign according to our data. Variant chr1-1013490-C-G is described in ClinVar as [Benign]. Clinvar id is 1185393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISG15	NM_005101.4 linkuse as main transcript			upstream_gene_variant		ENST00000649529.1	NP_005092.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ISG15	ENST00000624652.1 linkuse as main transcript	c.-21-494C>G	intron_variant	3		ENSP00000485313
ISG15	ENST00000624697.4 linkuse as main transcript	c.-21-494C>G	intron_variant	3		ENSP00000485643
ISG15	ENST00000649529.1 linkuse as main transcript		upstream_gene_variant		NM_005101.4	ENSP00000496832	P1

Frequencies

GnomAD3 genomes

AF:

0.898

AC:

136585

AN:

152022

Hom.:

62105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.742

Gnomad AMI

AF:

0.981

Gnomad AMR

AF:

0.936

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.968

Gnomad FIN

AF:

0.976

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.959

Gnomad OTH

AF:

0.907

GnomAD4 exome

AF:

0.954

AC:

1234934

AN:

1295018

Hom.:

590006

Cov.:

AF XY:

0.954

AC XY:

623299

AN XY:

653320

show subpopulations

Gnomad4 AFR exome

AF:

0.721

Gnomad4 AMR exome

AF:

0.954

Gnomad4 ASJ exome

AF:

0.903

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.960

Gnomad4 FIN exome

AF:

0.970

Gnomad4 NFE exome

AF:

0.961

Gnomad4 OTH exome

AF:

0.937

GnomAD4 genome

AF:

0.898

AC:

136643

AN:

152140

Hom.:

62121

Cov.:

AF XY:

0.900

AC XY:

66951

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.741

Gnomad4 AMR

AF:

0.936

Gnomad4 ASJ

AF:

0.910

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.968

Gnomad4 FIN

AF:

0.976

Gnomad4 NFE

AF:

0.959

Gnomad4 OTH

AF:

0.908

Alfa

AF:

0.926

Hom.:

3709

Bravo

AF:

0.888

Asia WGS

AF:

0.967

AC:

3364

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 14, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.53

DANN

Benign

0.47

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