rs1046129

Variant names:

• chr9-130707474-T-G
• rs1046129
• ENST00000819196.1:n.147+5374A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000819196.1(ENSG00000306514):​n.147+5374A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 152,184 control chromosomes in the GnomAD database, including 403 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 0.053 (403 hom., cov: 31)
• Consequence: ENSG00000306514 ENST00000819196.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 2 publications found

Genes affected

ENSG00000306514 (HGNC:):

EXOSC2 (HGNC:17097): (exosome component 2) Predicted to enable RNA binding activity. Involved in positive regulation of cell growth. Located in cytoplasm; nucleolus; and nucleoplasm. Part of nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

EXOSC2 Gene-Disease associations (from GenCC):

• retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000306514	ENST00000819196.1	n.147+5374A>C		intron_variant	Intron 1 of 1
EXOSC2	ENST00000691284.1	n.*898T>G		downstream_gene_variant				ENSP00000508620.1

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8063 AN: 152068 Hom.: 398 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0532 AC: 8096 AN: 152184 Hom.: 403 Cov.: 31 AF XY: 0.0523 AC XY: 3890 AN XY: 74400

African (AFR) AF: 0.137 AC: 5669 AN: 41492

American (AMR) AF: 0.0313 AC: 478 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5178

South Asian (SAS) AF: 0.00932 AC: 45 AN: 4826

European-Finnish (FIN) AF: 0.0192 AC: 204 AN: 10604

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0217 AC: 1475 AN: 68014

Other (OTH) AF: 0.0445 AC: 94 AN: 2110

Alfa AF: 0.0410 Hom.: 79

Bravo AF: 0.0578

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.14
PhyloP100		0.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1046129; hg19: chr9-133582861; COSMIC: COSV64911083;