8-9082213-G-A

Variant names:

• chr8-9082213-G-A
• rs10503389
• NM_001354638.2:c.808-6247G>A

Variant summary

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

The NM_001354638.2(ERI1):​c.808-6247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,022 control chromosomes in the GnomAD database, including 6,899 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 0.29 (6899 hom., cov: 32)
• Consequence: ERI1 NM_001354638.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 2 publications found

Genes affected

ERI1 (HGNC:23994): (exoribonuclease 1) Enables 3'-5' exonuclease activity. Predicted to be involved in exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ERI1 Gene-Disease associations (from GenCC):

• Hoxha-Aliu syndrome

  Inheritance: AR Classification: MODERATE Submitted by: G2P
• spondyloepimetaphyseal dysplasia, Guo-Campeau type

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERI1	NM_001354638.2	c.808-6247G>A		intron_variant	Intron 6 of 7		NP_001341567.1
ERI1	XM_047422402.1	c.808-6247G>A		intron_variant	Intron 6 of 7		XP_047278358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERI1	ENST00000520332.6	c.400-6247G>A		intron_variant	Intron 4 of 5	3		ENSP00000518572.1
ERI1	ENST00000518663.2	c.298-34135G>A		intron_variant	Intron 3 of 3	5		ENSP00000518573.1
ERI1	ENST00000522258.1	n.150-17646G>A		intron_variant	Intron 2 of 2	3
ERI1	ENST00000522612.2	n.52-6247G>A		intron_variant	Intron 1 of 3	3		ENSP00000518574.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44277 AN: 151904 Hom.: 6904 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.291 AC: 44277 AN: 152022 Hom.: 6899 Cov.: 32 AF XY: 0.289 AC XY: 21487 AN XY: 74300

African (AFR) AF: 0.233 AC: 9640 AN: 41456

American (AMR) AF: 0.265 AC: 4046 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3472

East Asian (EAS) AF: 0.0319 AC: 165 AN: 5168

South Asian (SAS) AF: 0.202 AC: 973 AN: 4816

European-Finnish (FIN) AF: 0.340 AC: 3596 AN: 10562

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23810 AN: 67948

Other (OTH) AF: 0.292 AC: 616 AN: 2110

Alfa AF: 0.293 Hom.: 4334

Bravo AF: 0.284

Asia WGS AF: 0.125 AC: 439 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.44
DANN	Benign	0.48
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs10503389; hg19: chr8-8939723;