Genetic Variant NM_001303233.2:c.-24-1796A>G (chr15-88637547-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001303233.2(ISG20):c.-24-1796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,058 control chromosomes in the GnomAD database, including 23,600 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 23570 hom., cov: 30)

Exomes 𝑓: 0.60 ( 30 hom. )

Consequence

ISG20
NM_001303233.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.472

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
ISG20	NM_001303233.2 link	c.-24-1796A>G	intron_variant	Intron 1 of 3	NP_001290162.1	Q96AZ6-1
ISG20	NM_001303234.2 link	c.-25+1255A>G	intron_variant	Intron 2 of 4	NP_001290163.1	Q96AZ6-1
ISG20	NM_001303235.2 link	c.-1681+1847A>G	intron_variant	Intron 1 of 2	NP_001290164.1
ISG20	NR_130134.2 link	n.69+1847A>G	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ISG20	ENST00000379224.10 link	c.-142+1255A>G	intron_variant	Intron 2 of 5	3	ENSP00000368526.6	Q96AZ6-1H3BLY5
ISG20	ENST00000560741.5 link	c.-25+1255A>G	intron_variant	Intron 1 of 3	5	ENSP00000453638.1	Q96AZ6-1
ISG20	ENST00000558992.1 link	n.*119A>G	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83840

AN:

151778

Hom.:

23546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.521

Gnomad AMR

AF:

0.601

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.605

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.601

Gnomad OTH

AF:

0.562

GnomAD4 exome

AF:

0.599

AC:

AN:

162

Hom.:

AF XY:

0.597

AC XY:

AN XY:

124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.600

AC:

AN:

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.620

AC:

AN:

108

Other (OTH)

AF:

0.444

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.552

AC:

83896

AN:

151896

Hom.:

23570

Cov.:

AF XY:

0.552

AC XY:

40938

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.446

AC:

18460

AN:

41400

American (AMR)

AF:

0.601

AC:

9180

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1976

AN:

3470

East Asian (EAS)

AF:

0.606

AC:

3115

AN:

5142

South Asian (SAS)

AF:

0.587

AC:

2826

AN:

4816

European-Finnish (FIN)

AF:

0.536

AC:

5644

AN:

10524

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.601

AC:

40875

AN:

67966

Other (OTH)

AF:

0.560

AC:

1179

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1897

3795

5692

7590

9487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.587

Hom.:

76412

Bravo

AF:

0.552

Asia WGS

AF:

0.559

AC:

1944

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.5

(source)

DANN

Benign

0.31

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over