rs2342286

Positions:

• chr3-129158157-C-G
• chr3-129158157-C-T

Variant summary

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

The NM_020701.4(ISY1):​c.78+351G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 141,152 control chromosomes in the GnomAD database, including 1,351 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 0.078 (1351 hom., cov: 28)
• Consequence: ISY1 NM_020701.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISY1	NM_020701.4	c.78+351G>C		intron_variant		ENST00000393295.8	NP_065752.1
ISY1-RAB43	NM_001204890.2	c.78+351G>C		intron_variant			NP_001191819.1
ISY1	NM_001199469.2	c.78+351G>C		intron_variant			NP_001186398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISY1	ENST00000393295.8	c.78+351G>C		intron_variant		1	NM_020701.4	ENSP00000376973	P1
ISY1	ENST00000273541.12	c.78+351G>C		intron_variant		1		ENSP00000273541
ISY1	ENST00000393292.7	c.78+351G>C		intron_variant		5		ENSP00000376970
ISY1	ENST00000485703.1	c.78+351G>C		intron_variant, NMD_transcript_variant		5		ENSP00000422403

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 10944 AN: 141136 Hom.: 1347 Cov.: 28

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.00669

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00136

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0364

Gnomad NFE AF: 0.00127

Gnomad OTH AF: 0.0616

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

GnomAD4 genome AF: 0.0776 AC: 10952 AN: 141152 Hom.: 1351 Cov.: 28 AF XY: 0.0741 AC XY: 5072 AN XY: 68488

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.00669

Gnomad4 EAS AF: 0.000205

Gnomad4 SAS AF: 0.00114

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00127

Gnomad4 OTH AF: 0.0613

Alfa AF: 0.00213 Hom.: 2

Bravo AF: 0.0859

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs2342286; hg19: chr3-128877000;