8-9082321-C-G

Variant names:

• chr8-9082321-C-G
• rs6987277
• NM_001354638.2:c.808-6139C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001354638.2(ERI1):​c.808-6139C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,232 control chromosomes in the GnomAD database, including 1,609 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 0.14 (1609 hom., cov: 32)
• Consequence: ERI1 NM_001354638.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354638.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERI1	NM_001354638.2		c.808-6139C>G		intron	N/A	NP_001341567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERI1	ENST00000520332.6	TSL:3	c.400-6139C>G		intron	N/A	ENSP00000518572.1
	ERI1	ENST00000518663.2	TSL:5	c.298-34027C>G		intron	N/A	ENSP00000518573.1
	ERI1	ENST00000522258.1	TSL:3	n.150-17538C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20931 AN: 152114 Hom.: 1606 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.138 AC: 20933 AN: 152232 Hom.: 1609 Cov.: 32 AF XY: 0.132 AC XY: 9861 AN XY: 74438

African (AFR) AF: 0.121 AC: 5037 AN: 41524

American (AMR) AF: 0.113 AC: 1721 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.104 AC: 503 AN: 4830

European-Finnish (FIN) AF: 0.0844 AC: 896 AN: 10610

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11480 AN: 67996

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.0790 Hom.: 93

Bravo AF: 0.136

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		0.87

Splicing

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

Other links and lift over

dbSNP: rs6987277; hg19: chr8-8939831;