Variant chr1-1013466-T-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000624697.4(ISG15):c.-21-517dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 58856 hom., cov: 0)

Exomes 𝑓: 0.96 ( 501221 hom. )

Consequence

ISG15
ENST00000624697.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0200

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 -16 ACMG points.

BP6

Variant 1-1013466-T-TA is Benign according to our data. Variant chr1-1013466-T-TA is described in ClinVar as [Benign]. Clinvar id is 1185392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
ISG15	ENST00000624652.1 linkuse as main transcript	c.-21-517dup	intron_variant	3
ISG15	ENST00000624697.4 linkuse as main transcript	c.-21-517dup	intron_variant	3
ISG15	ENST00000649529.1 linkuse as main transcript		upstream_gene_variant		NM_005101.4	P1

Frequencies

GnomAD3 genomes

AF:

0.864

AC:

131341

AN:

152028

Hom.:

58852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.595

Gnomad AMI

AF:

0.994

Gnomad AMR

AF:

0.931

Gnomad ASJ

AF:

0.928

Gnomad EAS

AF:

0.951

Gnomad SAS

AF:

0.962

Gnomad FIN

AF:

0.986

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.974

Gnomad OTH

AF:

0.882

GnomAD4 exome

AF:

0.959

AC:

1039282

AN:

1083744

Hom.:

501221

Cov.:

AF XY:

0.960

AC XY:

534862

AN XY:

557114

show subpopulations

Gnomad4 AFR exome

AF:

0.571

Gnomad4 AMR exome

AF:

0.951

Gnomad4 ASJ exome

AF:

0.922

Gnomad4 EAS exome

AF:

0.967

Gnomad4 SAS exome

AF:

0.957

Gnomad4 FIN exome

AF:

0.985

Gnomad4 NFE exome

AF:

0.974

Gnomad4 OTH exome

AF:

0.935

GnomAD4 genome

AF:

0.863

AC:

131371

AN:

152146

Hom.:

58856

Cov.:

AF XY:

0.866

AC XY:

64448

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.594

Gnomad4 AMR

AF:

0.931

Gnomad4 ASJ

AF:

0.928

Gnomad4 EAS

AF:

0.951

Gnomad4 SAS

AF:

0.962

Gnomad4 FIN

AF:

0.986

Gnomad4 NFE

AF:

0.974

Gnomad4 OTH

AF:

0.883

Alfa

AF:

0.907

Hom.:

7814

Bravo

AF:

0.845

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 83% of patients studied by a panel of primary immunodeficiencies. Number of patients: 80. Only high quality variants are reported. -

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

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