chr1-1013549-GGCCCACAGCCCACA-G

Variant names:

• chr1-1013549-GGCCCACAGCCCACA-G
• NM_005101.4:c.-14_-1delCACAGCCCACAGCC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_005101.4(ISG15):​c.-14_-1delCACAGCCCACAGCC variant causes a start retained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ISG15 NM_005101.4 start_retained
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.796

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-1013549-GGCCCACAGCCCACA-G is Benign according to our data. Variant chr1-1013549-GGCCCACAGCCCACA-G is described in ClinVar as [Likely_benign]. Clinvar id is 3040451.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISG15	NM_005101.4	c.-14_-1delCACAGCCCACAGCC		start_retained_variant	Exon 1 of 2	ENST00000649529.1	NP_005092.1
ISG15	NM_005101.4	c.-14_-1delCACAGCCCACAGCC		5_prime_UTR_variant	Exon 1 of 2	ENST00000649529.1	NP_005092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISG15	ENST00000649529	c.-14_-1delCACAGCCCACAGCC		start_retained_variant	Exon 1 of 2		NM_005101.4	ENSP00000496832.1
ISG15	ENST00000649529	c.-14_-1delCACAGCCCACAGCC		5_prime_UTR_variant	Exon 1 of 2		NM_005101.4	ENSP00000496832.1
ISG15	ENST00000624697.4	c.-21-424_-21-411delCACAGCCCACAGCC		intron_variant	Intron 2 of 2	3		ENSP00000485643.1
ISG15	ENST00000624652.1	c.-21-424_-21-411delCACAGCCCACAGCC		intron_variant	Intron 2 of 2	3		ENSP00000485313.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ISG15-related disorder Benign:1

Sep 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-948929;