rs6074585

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080826.2(ISM1):​c.877+2092G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,184 control chromosomes in the GnomAD database, including 1,356 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 ( 1356 hom., cov: 32)

Consequence

ISM1
NM_080826.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.167
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ISM1NM_080826.2 linkc.877+2092G>C intron_variant Intron 5 of 5 ENST00000262487.5 NP_543016.1 B1AKI9
ISM1XM_017027680.2 linkc.877+2092G>C intron_variant Intron 5 of 6 XP_016883169.1
TASP1XR_001754319.3 linkn.1369+21415C>G intron_variant Intron 14 of 14
TASP1XR_007067463.1 linkn.1369+21415C>G intron_variant Intron 14 of 14

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ISM1ENST00000262487.5 linkc.877+2092G>C intron_variant Intron 5 of 5 5 NM_080826.2 ENSP00000262487.3 B1AKI9

Frequencies

GnomAD3 genomes
AF:
0.118
AC:
18002
AN:
152066
Hom.:
1355
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0629
Gnomad AMI
AF:
0.175
Gnomad AMR
AF:
0.125
Gnomad ASJ
AF:
0.292
Gnomad EAS
AF:
0.000579
Gnomad SAS
AF:
0.0786
Gnomad FIN
AF:
0.101
Gnomad MID
AF:
0.180
Gnomad NFE
AF:
0.154
Gnomad OTH
AF:
0.155
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.118
AC:
17990
AN:
152184
Hom.:
1356
Cov.:
32
AF XY:
0.114
AC XY:
8503
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0627
Gnomad4 AMR
AF:
0.125
Gnomad4 ASJ
AF:
0.292
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.0778
Gnomad4 FIN
AF:
0.101
Gnomad4 NFE
AF:
0.154
Gnomad4 OTH
AF:
0.153
Alfa
AF:
0.0512
Hom.:
54
Bravo
AF:
0.119
Asia WGS
AF:
0.0470
AC:
165
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
2.9
DANN
Benign
0.64

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6074585; hg19: chr20-13275202; API