1-1013466-T-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0200

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]

ACMG classification

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			upstream_gene_variant		ENST00000649529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISG15	ENST00000624652.1	c.-21-517dup		intron_variant		3
ISG15	ENST00000624697.4	c.-21-517dup		intron_variant		3
ISG15	ENST00000649529.1			upstream_gene_variant			NM_005101.4	P1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131341 AN: 152028 Hom.: 58852 Cov.: 0

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.: 16 AF XY: 0.960 AC XY: 534862 AN XY: 557114

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.: 0 AF XY: 0.866 AC XY: 64448 AN XY: 74392

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

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

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

Other links and lift over

dbSNP: rs3841266; hg19: chr1-948846;