rs1407335

Positions:

• chr20-13242211-A-C
• chr20-13242211-A-G

Variant summary

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

The NM_080826.2(ISM1):​c.138+20297A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,924 control chromosomes in the GnomAD database, including 9,348 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 0.34 (9348 hom., cov: 32)
• Consequence: ISM1 NM_080826.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISM1	NM_080826.2	c.138+20297A>C		intron_variant		ENST00000262487.5	NP_543016.1
ISM1	XM_017027680.2	c.138+20297A>C		intron_variant			XP_016883169.1
TASP1	XR_007067463.1	n.25341T>G		non_coding_transcript_exon_variant	15/15
TASP1	XR_001754319.3	n.1369+73759T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISM1	ENST00000262487.5	c.138+20297A>C		intron_variant		5	NM_080826.2	ENSP00000262487.3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51706 AN: 151806 Hom.: 9326 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.341 AC: 51776 AN: 151924 Hom.: 9348 Cov.: 32 AF XY: 0.344 AC XY: 25529 AN XY: 74246

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.334

Alfa AF: 0.276 Hom.: 3363

Bravo AF: 0.350

Asia WGS AF: 0.404 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.48
DANN	Benign	0.54

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: rs1407335; hg19: chr20-13222858;