8-9032588-C-T

Variant names:

• chr8-9032588-C-T
• rs1045529
• NM_153332.4:c.*2554C>T

Variant summary

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

The NM_153332.4(ERI1):​c.*2554C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,002 control chromosomes in the GnomAD database, including 13,740 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 0.39 (13740 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ERI1 NM_153332.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 18 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153332.4. 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_153332.4	MANE Select	c.*2554C>T		3_prime_UTR	Exon 7 of 7	NP_699163.2
	ERI1	NM_001354635.2		c.*2554C>T		3_prime_UTR	Exon 7 of 7	NP_001341564.1
	ERI1	NM_001354636.2		c.*2554C>T		3_prime_UTR	Exon 8 of 8	NP_001341565.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERI1	ENST00000250263.8	TSL:1 MANE Select	c.*2554C>T		3_prime_UTR	Exon 7 of 7	ENSP00000250263.7
	ERI1	ENST00000877111.1		c.*2554C>T		3_prime_UTR	Exon 7 of 7	ENSP00000547170.1
	ERI1	ENST00000519292.5	TSL:2	c.*87C>T		3_prime_UTR	Exon 8 of 8	ENSP00000430190.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59486 AN: 151884 Hom.: 13715 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.413

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.392 AC: 59530 AN: 152002 Hom.: 13740 Cov.: 32 AF XY: 0.404 AC XY: 30014 AN XY: 74300

African (AFR) AF: 0.155 AC: 6404 AN: 41426

American (AMR) AF: 0.563 AC: 8596 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1152 AN: 3466

East Asian (EAS) AF: 0.687 AC: 3556 AN: 5176

South Asian (SAS) AF: 0.558 AC: 2687 AN: 4818

European-Finnish (FIN) AF: 0.534 AC: 5632 AN: 10542

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30045 AN: 67976

Other (OTH) AF: 0.420 AC: 886 AN: 2112

Alfa AF: 0.396 Hom.: 10567

Bravo AF: 0.387

Asia WGS AF: 0.592 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.74
PhyloP100		0.0040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1045529; hg19: chr8-8890098;