1-156727264-T-C

Variant names:

• chr1-156727264-T-C
• rs3795737
• NM_001370150.2:c.389A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370150.2(ISG20L2):​c.389A>G​(p.Asn130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 1,613,996 control chromosomes in the GnomAD database, including 8,046 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N130H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.11 (1281 hom., cov: 32)
  • Exomes 𝑓: 0.075 (6765 hom.)
• Consequence: ISG20L2 NM_001370150.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371
• Publications: 28 publications found

Genes affected

ISG20L2 (HGNC:25745): (interferon stimulated exonuclease gene 20 like 2) This gene encodes a 3'-5' exoribonuclease that may be involved in the processing of the 12S pre-rRNA. Pseudogenes have been identified on chromosomes 6 and 11. [provided by RefSeq, Dec 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.003397286).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISG20L2	NM_001370150.2	c.389A>G	p.Asn130Ser	missense_variant	Exon 2 of 4	ENST00000368219.2	NP_001357079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISG20L2	ENST00000368219.2	c.389A>G	p.Asn130Ser	missense_variant	Exon 2 of 4	5	NM_001370150.2	ENSP00000357202.2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16807 AN: 152050 Hom.: 1277 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.123 AC: 31009 AN: 251348 AF XY: 0.112

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.166

Gnomad FIN exome AF: 0.0491

Gnomad NFE exome AF: 0.0572

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0752 AC: 109897 AN: 1461828 Hom.: 6765 Cov.: 33 AF XY: 0.0745 AC XY: 54182 AN XY: 727216

African (AFR) AF: 0.177 AC: 5933 AN: 33480

American (AMR) AF: 0.347 AC: 15522 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2989 AN: 26136

East Asian (EAS) AF: 0.138 AC: 5485 AN: 39700

South Asian (SAS) AF: 0.107 AC: 9229 AN: 86258

European-Finnish (FIN) AF: 0.0490 AC: 2616 AN: 53364

Middle Eastern (MID) AF: 0.0969 AC: 559 AN: 5768

European-Non Finnish (NFE) AF: 0.0559 AC: 62182 AN: 1112002

Other (OTH) AF: 0.0891 AC: 5382 AN: 60396

GnomAD4 genome AF: 0.111 AC: 16823 AN: 152168 Hom.: 1281 Cov.: 32 AF XY: 0.112 AC XY: 8306 AN XY: 74418

African (AFR) AF: 0.171 AC: 7113 AN: 41512

American (AMR) AF: 0.215 AC: 3277 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3470

East Asian (EAS) AF: 0.167 AC: 863 AN: 5172

South Asian (SAS) AF: 0.115 AC: 553 AN: 4820

European-Finnish (FIN) AF: 0.0507 AC: 538 AN: 10614

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0551 AC: 3749 AN: 67996

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.0864 Hom.: 1118

Bravo AF: 0.131

TwinsUK AF: 0.0577 AC: 214

ALSPAC AF: 0.0545 AC: 210

ESP6500AA AF: 0.174 AC: 766

ESP6500EA AF: 0.0588 AC: 506

ExAC AF: 0.115 AC: 13914

Asia WGS AF: 0.154 AC: 534 AN: 3478

EpiCase AF: 0.0607

EpiControl AF: 0.0638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.49
DEOGEN2	Benign	0.00080	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.32	.;T
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		0.37
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.090	N;N
REVEL	Benign	0.048
Sift	Benign	0.39	T;T
Sift4G	Benign	0.87	T;T
Polyphen		0.0	B;B
Vest4		0.0070
MPC		0.23
ClinPred		0.0028	T
GERP RS		0.67
Varity_R		0.066
gMVP		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3795737; hg19: chr1-156697056; COSMIC: COSV57459868; COSMIC: COSV57459868;