Variant 1-1013541-T-C 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 NM_005101.4(ISG15):c.-33T>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 0.95 in 1,612,360 control chromosomes in the GnomAD database, including 730,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 62181 hom., cov: 33)

Exomes 𝑓: 0.96 ( 668050 hom. )

Consequence

ISG15
NM_005101.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.966

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=-0.93).

BP6

Variant 1-1013541-T-C is Benign according to our data. Variant chr1-1013541-T-C is described in ClinVar as [Benign]. Clinvar id is 1185394.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	UniProt
ISG15	NM_005101.4 linkuse as main transcript	c.-33T>C		5_prime_UTR_variant	1/2	ENST00000649529.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
ISG15	ENST00000649529.1 linkuse as main transcript	c.-33T>C	5_prime_UTR_variant	1/2		NM_005101.4	P1
ISG15	ENST00000624652.1 linkuse as main transcript	c.-21-443T>C	intron_variant		3
ISG15	ENST00000624697.4 linkuse as main transcript	c.-21-443T>C	intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.899

AC:

136681

AN:

152066

Hom.:

62165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.743

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.936

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.968

Gnomad FIN

AF:

0.975

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.959

Gnomad OTH

AF:

0.907

GnomAD3 exomes

AF:

0.946

AC:

236864

AN:

250474

Hom.:

112515

AF XY:

0.949

AC XY:

128803

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.738

Gnomad AMR exome

AF:

0.958

Gnomad ASJ exome

AF:

0.904

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.961

Gnomad FIN exome

AF:

0.971

Gnomad NFE exome

AF:

0.958

Gnomad OTH exome

AF:

0.938

GnomAD4 exome

AF:

0.956

AC:

1395472

AN:

1460178

Hom.:

668050

Cov.:

AF XY:

0.956

AC XY:

694436

AN XY:

726480

show subpopulations

Gnomad4 AFR exome

AF:

0.728

Gnomad4 AMR exome

AF:

0.954

Gnomad4 ASJ exome

AF:

0.904

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.961

Gnomad4 FIN exome

AF:

0.970

Gnomad4 NFE exome

AF:

0.962

Gnomad4 OTH exome

AF:

0.939

GnomAD4 genome

AF:

0.899

AC:

136739

AN:

152182

Hom.:

62181

Cov.:

AF XY:

0.900

AC XY:

66993

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.742

Gnomad4 AMR

AF:

0.936

Gnomad4 ASJ

AF:

0.910

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.968

Gnomad4 FIN

AF:

0.975

Gnomad4 NFE

AF:

0.959

Gnomad4 OTH

AF:

0.908

Alfa

AF:

0.934

Hom.:

44619

Bravo

AF:

0.889

Asia WGS

AF:

0.966

AC:

3361

AN:

3478

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 02, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 96. 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

BayesDel_noAF

Benign

-0.93

Cadd

Benign

3.2

Dann

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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