rs8038865

Positions:

• chr15-88637871-G-C
• chr15-88637871-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303233.2(ISG20):​c.-24-1472G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,020 control chromosomes in the GnomAD database, including 9,509 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 0.32 (9509 hom., cov: 32)
• Consequence: ISG20 NM_001303233.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISG20	NM_001303233.2	c.-24-1472G>C		intron_variant
ISG20	NM_001303234.2	c.-24-1472G>C		intron_variant
ISG20	NM_001303235.2	c.-1681+2171G>C		intron_variant
ISG20	NR_130134.2	n.69+2171G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISG20	ENST00000379224.10	c.-141-1089G>C		intron_variant		3		P1
ISG20	ENST00000560741.5	c.-24-1472G>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49325 AN: 151902 Hom.: 9495 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.325 AC: 49380 AN: 152020 Hom.: 9509 Cov.: 32 AF XY: 0.320 AC XY: 23750 AN XY: 74320

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.312

Alfa AF: 0.155 Hom.: 281

Bravo AF: 0.330

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.84

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

Other links and lift over

dbSNP: rs8038865; hg19: chr15-89181102;