NM_001354638.2:c.808-5935C>A

Variant names:

• chr8-9082525-C-A
• rs6601286
• NM_001354638.2:c.808-5935C>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.808-5935C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,146 control chromosomes in the GnomAD database, including 1,654 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 (1654 hom., cov: 32)
• Consequence: ERI1 NM_001354638.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• Publications: 5 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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERI1	NM_001354638.2	c.808-5935C>A		intron_variant	Intron 6 of 7		NP_001341567.1
ERI1	XM_047422402.1	c.808-5935C>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.400-5935C>A		intron_variant	Intron 4 of 5	3		ENSP00000518572.1
ERI1	ENST00000518663.2	c.298-33823C>A		intron_variant	Intron 3 of 3	5		ENSP00000518573.1
ERI1	ENST00000522258.1	n.150-17334C>A		intron_variant	Intron 2 of 2	3
ERI1	ENST00000522612.2	n.52-5935C>A		intron_variant	Intron 1 of 3	3		ENSP00000518574.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21257 AN: 152028 Hom.: 1651 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.140 AC: 21258 AN: 152146 Hom.: 1654 Cov.: 32 AF XY: 0.135 AC XY: 10023 AN XY: 74384

African (AFR) AF: 0.131 AC: 5423 AN: 41496

American (AMR) AF: 0.114 AC: 1742 AN: 15294

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

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5194

South Asian (SAS) AF: 0.104 AC: 499 AN: 4796

European-Finnish (FIN) AF: 0.0848 AC: 899 AN: 10604

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11395 AN: 67976

Other (OTH) AF: 0.152 AC: 321 AN: 2110

Alfa AF: 0.0826 Hom.: 104

Bravo AF: 0.138

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs6601286; hg19: chr8-8940035;