Variant 1-1013855-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005101.4(ISG15):c.4-129G>A 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 1,297,970 control chromosomes in the GnomAD database, including 585,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.89 ( 61792 hom., cov: 33)

Exomes 𝑓: 0.96 ( 523932 hom. )

Consequence

ISG15
NM_005101.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.255

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:

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=-0.77).

BP6

Variant 1-1013855-G-A is Benign according to our data. Variant chr1-1013855-G-A is described in ClinVar as [Benign]. Clinvar id is 1185395.Status of the report is criteria_provided_single_submitter, 1 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	c.4-129G>A		intron_variant		ENST00000649529.1	NP_005092.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ISG15	ENST00000649529.1 linkuse as main transcript	c.4-129G>A	intron_variant		NM_005101.4	ENSP00000496832	P1
ISG15	ENST00000624652.1 linkuse as main transcript	c.-21-129G>A	intron_variant	3		ENSP00000485313
ISG15	ENST00000624697.4 linkuse as main transcript	c.-21-129G>A	intron_variant	3		ENSP00000485643

Frequencies

GnomAD3 genomes

AF:

0.895

AC:

136143

AN:

152102

Hom.:

61776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.731

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.933

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:

0.906

GnomAD4 exome

AF:

0.955

AC:

1094615

AN:

1145750

Hom.:

523932

AF XY:

0.955

AC XY:

542931

AN XY:

568218

show subpopulations

Gnomad4 AFR exome

AF:

0.715

Gnomad4 AMR exome

AF:

0.951

Gnomad4 ASJ exome

AF:

0.904

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.961

Gnomad4 FIN exome

AF:

0.969

Gnomad4 NFE exome

AF:

0.962

Gnomad4 OTH exome

AF:

0.939

GnomAD4 genome

AF:

0.895

AC:

136202

AN:

152220

Hom.:

61792

Cov.:

AF XY:

0.897

AC XY:

66741

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.730

Gnomad4 AMR

AF:

0.933

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:

0.907

Alfa

AF:

0.921

Hom.:

8139

Bravo

AF:

0.884

Asia WGS

AF:

0.968

AC:

3366

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.77

CADD

Benign

2.0

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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