rs1482409

Variant summary

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

The NM_020701.4(ISY1):​c.27-125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,304,938 control chromosomes in the GnomAD database, including 825 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 0.034 ( 208 hom., cov: 32)
Exomes 𝑓: 0.012 ( 617 hom. )

Consequence

ISY1
NM_020701.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.739
Variant links:
Genes affected
ISY1 (HGNC:29201): (ISY1 splicing factor homolog) Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleus. Part of U2-type catalytic step 1 spliceosome and catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ISY1NM_020701.4 linkuse as main transcriptc.27-125A>G intron_variant ENST00000393295.8
ISY1-RAB43NM_001204890.2 linkuse as main transcriptc.27-125A>G intron_variant
ISY1NM_001199469.2 linkuse as main transcriptc.27-125A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ISY1ENST00000393295.8 linkuse as main transcriptc.27-125A>G intron_variant 1 NM_020701.4 P1Q9ULR0-3
ISY1ENST00000273541.12 linkuse as main transcriptc.27-125A>G intron_variant 1 Q9ULR0-2
ISY1ENST00000393292.7 linkuse as main transcriptc.27-125A>G intron_variant 5
ISY1ENST00000485703.1 linkuse as main transcriptc.27-125A>G intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0344
AC:
5233
AN:
152158
Hom.:
207
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0885
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0143
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.109
Gnomad SAS
AF:
0.0962
Gnomad FIN
AF:
0.0171
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00131
Gnomad OTH
AF:
0.0215
GnomAD4 exome
AF:
0.0119
AC:
13666
AN:
1152662
Hom.:
617
AF XY:
0.0139
AC XY:
8044
AN XY:
577556
show subpopulations
Gnomad4 AFR exome
AF:
0.0951
Gnomad4 AMR exome
AF:
0.00534
Gnomad4 ASJ exome
AF:
0.000843
Gnomad4 EAS exome
AF:
0.0820
Gnomad4 SAS exome
AF:
0.0845
Gnomad4 FIN exome
AF:
0.0171
Gnomad4 NFE exome
AF:
0.000922
Gnomad4 OTH exome
AF:
0.0167
GnomAD4 genome
AF:
0.0344
AC:
5239
AN:
152276
Hom.:
208
Cov.:
32
AF XY:
0.0362
AC XY:
2696
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0884
Gnomad4 AMR
AF:
0.0144
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.109
Gnomad4 SAS
AF:
0.0958
Gnomad4 FIN
AF:
0.0171
Gnomad4 NFE
AF:
0.00131
Gnomad4 OTH
AF:
0.0213
Alfa
AF:
0.00913
Hom.:
35
Bravo
AF:
0.0346
Asia WGS
AF:
0.0790
AC:
276
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
0.17
DANN
Benign
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1482409; hg19: chr3-128877527; COSMIC: COSV56440224; COSMIC: COSV56440224; API