rs2062125

Positions:

• chr3-129143375-G-A
• chr3-129143375-G-T

Variant summary

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

The NM_020701.4(ISY1):​c.300+2386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 151,608 control chromosomes in the GnomAD database, including 59,751 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 0.88 (59751 hom., cov: 27)
• Consequence: ISY1 NM_020701.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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:42969): (ISY1-RAB43 readthrough) This locus represents naturally occurring read-through transcription between the neighboring ISY1 (ISY1 splicing factor homolog) and RAB43 (RAB43, member RAS oncogene family) gene on chromosome 3. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product, but its C-terminus is distinct due to a frameshift relative to the downstream gene. [provided by RefSeq, Mar 2011]

ISY1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISY1	NM_020701.4	c.300+2386C>T		intron_variant		ENST00000393295.8	NP_065752.1
ISY1-RAB43	NM_001204890.2	c.300+2386C>T		intron_variant			NP_001191819.1
ISY1	NM_001199469.2	c.300+2386C>T		intron_variant			NP_001186398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISY1	ENST00000393295.8	c.300+2386C>T		intron_variant		1	NM_020701.4	ENSP00000376973.4
ISY1-RAB43	ENST00000418265.1	c.300+2386C>T		intron_variant		2		ENSP00000411822.1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133304 AN: 151490 Hom.: 59746 Cov.: 27

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.907

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.880 AC: 133340 AN: 151608 Hom.: 59751 Cov.: 27 AF XY: 0.879 AC XY: 65118 AN XY: 74102

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.962

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.974

Gnomad4 OTH AF: 0.898

Alfa AF: 0.923 Hom.: 7672

Bravo AF: 0.867

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.55

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: rs2062125; hg19: chr3-128862218;