rs1223271

Variant names:

• chr20-13316265-G-A
• rs1223271
• XM_017027680.2:c.878-8801G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-13316265-G-A
• chr20-13316265-G-C

Variant summary

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

The XM_017027680.2(ISM1):​c.878-8801G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 151,810 control chromosomes in the GnomAD database, including 1,700 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 (1700 hom., cov: 32)
• Consequence: ISM1 XM_017027680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• Publications: 16 publications found

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]

TASP1 Gene-Disease associations (from GenCC):

• Suleiman-El-Hattab syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISM1	XM_017027680.2	c.878-8801G>A		intron_variant	Intron 5 of 6		XP_016883169.1
TASP1	XM_047440269.1	c.1171-210C>T		intron_variant	Intron 13 of 13		XP_047296225.1
TASP1	XR_001754319.3	n.1284-210C>T		intron_variant	Intron 13 of 14
TASP1	XR_007067463.1	n.1284-210C>T		intron_variant	Intron 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18485 AN: 151694 Hom.: 1698 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.122 AC: 18483 AN: 151810 Hom.: 1700 Cov.: 32 AF XY: 0.128 AC XY: 9473 AN XY: 74198

African (AFR) AF: 0.0258 AC: 1070 AN: 41498

American (AMR) AF: 0.129 AC: 1963 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3458

East Asian (EAS) AF: 0.430 AC: 2229 AN: 5178

South Asian (SAS) AF: 0.309 AC: 1489 AN: 4812

European-Finnish (FIN) AF: 0.147 AC: 1545 AN: 10540

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9338 AN: 67760

Other (OTH) AF: 0.135 AC: 283 AN: 2100

Alfa AF: 0.136 Hom.: 5270

Bravo AF: 0.118

Asia WGS AF: 0.342 AC: 1188 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.25
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1223271; hg19: chr20-13296912;