20-13319088-G-A

Position:

• chr20-13319088-G-A

Variant summary

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

The XM_017027680.2(ISM1):​c.878-5978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,150 control chromosomes in the GnomAD database, including 1,528 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 0.12 (1528 hom., cov: 32)
• Consequence: ISM1 XM_017027680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

ISM1 (HGNC:16213): (isthmin 1) Predicted to be involved in negative regulation of angiogenesis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

TASP1 (HGNC:15859): (taspase 1) This gene encodes an endopeptidase that cleaves specific substrates following aspartate residues. The encoded protein undergoes posttranslational autoproteolytic processing to generate alpha and beta subunits, which reassemble into the active alpha2-beta2 heterotetramer. It is required to cleave MLL, a protein required for the maintenance of HOX gene expression, and TFIIA, a basal transcription factor. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISM1	XM_017027680.2	c.878-5978G>A		intron_variant			XP_016883169.1
TASP1	XM_047440269.1	c.1171-3033C>T		intron_variant			XP_047296225.1
		n.13319088G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18105 AN: 152032 Hom.: 1528 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0879

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.119 AC: 18109 AN: 152150 Hom.: 1528 Cov.: 32 AF XY: 0.117 AC XY: 8694 AN XY: 74392

Gnomad4 AFR AF: 0.0315

Gnomad4 AMR AF: 0.0880

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.0625

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.107

Alfa AF: 0.159 Hom.: 975

Bravo AF: 0.107

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13433297; hg19: chr20-13299735;