NM_001354638.2:c.808-2540A>T

Variant names:

• chr8-9085920-A-T
• rs6601288
• NM_001354638.2:c.808-2540A>T

Variant summary

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

The NM_001354638.2(ERI1):​c.808-2540A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,944 control chromosomes in the GnomAD database, including 35,795 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 0.67 (35795 hom., cov: 31)
• Consequence: ERI1 NM_001354638.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 8 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERI1	NM_001354638.2	c.808-2540A>T		intron_variant	Intron 6 of 7		NP_001341567.1
ERI1	XM_047422402.1	c.808-2540A>T		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.400-2540A>T		intron_variant	Intron 4 of 5	3		ENSP00000518572.1
ERI1	ENST00000518663.2	c.298-30428A>T		intron_variant	Intron 3 of 3	5		ENSP00000518573.1
ERI1	ENST00000522258.1	n.150-13939A>T		intron_variant	Intron 2 of 2	3
ERI1	ENST00000522612.2	n.52-2540A>T		intron_variant	Intron 1 of 3	3		ENSP00000518574.1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101620 AN: 151826 Hom.: 35776 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.669 AC: 101667 AN: 151944 Hom.: 35795 Cov.: 31 AF XY: 0.654 AC XY: 48538 AN XY: 74230

African (AFR) AF: 0.798 AC: 33105 AN: 41494

American (AMR) AF: 0.529 AC: 8064 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2611 AN: 3466

East Asian (EAS) AF: 0.0792 AC: 408 AN: 5150

South Asian (SAS) AF: 0.496 AC: 2390 AN: 4816

European-Finnish (FIN) AF: 0.543 AC: 5703 AN: 10508

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47071 AN: 67944

Other (OTH) AF: 0.658 AC: 1390 AN: 2112

Alfa AF: 0.704 Hom.: 4720

Bravo AF: 0.666

Asia WGS AF: 0.324 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.65
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs6601288; hg19: chr8-8943430;