rs1482409

Positions:

• chr3-129158684-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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]

ISY1-RAB43 (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 (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
ISY1	NM_020701.4	c.27-125A>G		intron_variant		ENST00000393295.8
ISY1-RAB43	NM_001204890.2	c.27-125A>G		intron_variant
ISY1	NM_001199469.2	c.27-125A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISY1	ENST00000393295.8	c.27-125A>G		intron_variant		1	NM_020701.4	P1
ISY1	ENST00000273541.12	c.27-125A>G		intron_variant		1
ISY1	ENST00000393292.7	c.27-125A>G		intron_variant		5
ISY1	ENST00000485703.1	c.27-125A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5233 AN: 152158 Hom.: 207 Cov.: 32

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

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

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

Other links and lift over

dbSNP: rs1482409; hg19: chr3-128877527; COSMIC: COSV56440224; COSMIC: COSV56440224;