Variant chr15-88639462-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001303236.2(ISG20):c.-1813C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,614,116 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 35 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 43 hom. )

Consequence

ISG20
NM_001303236.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.171

Variant links:

Genes affected

ISG20 (HGNC:6130): (interferon stimulated exonuclease gene 20) Enables 3'-5' exonuclease activity and RNA binding activity. Involved in defense response to virus; negative regulation of viral genome replication; and nucleobase-containing compound catabolic process. Located in cytoplasm and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ISG20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 15-88639462-C-T is Benign according to our data. Variant chr15-88639462-C-T is described in ClinVar as [Benign]. Clinvar id is 789078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1839/152272) while in subpopulation AFR AF= 0.0394 (1638/41558). AF 95% confidence interval is 0.0378. There are 35 homozygotes in gnomad4. There are 876 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISG20	NM_002201.6 link	c.96C>T	p.Asn32Asn	synonymous_variant	2/4	ENST00000306072.10	NP_002192.2	Q96AZ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISG20	ENST00000306072.10 link	c.96C>T	p.Asn32Asn	synonymous_variant	2/4	1	NM_002201.6	ENSP00000306565.5		Q96AZ6-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1831

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00395

AC:

993

AN:

251230

Hom.:

AF XY:

0.00304

AC XY:

413

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.0424

Gnomad AMR exome

AF:

0.00550

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000687

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00207

AC:

3019

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

1435

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0453

Gnomad4 AMR exome

AF:

0.00586

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000745

Gnomad4 OTH exome

AF:

0.00550

GnomAD4 genome

AF:

0.0121

AC:

1839

AN:

152272

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

876

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0394

Gnomad4 AMR

AF:

0.00791

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00588

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.6

DANN

Benign

0.83

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