8-9007961-T-TTG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_153332.4(ERI1):c.109-8_109-7insGT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,298,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERI1 NM_153332.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.314

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-9007961-T-TTG is Benign according to our data. Variant chr8-9007961-T-TTG is described in ClinVar as [Likely_benign]. Clinvar id is 731735.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERI1	NM_153332.4	c.109-8_109-7insGT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000250263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERI1	ENST00000250263.8	c.109-8_109-7insGT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_153332.4	P1
ERI1	ENST00000519292.5	c.109-8_109-7insGT		splice_polypyrimidine_tract_variant, intron_variant		2		P1
ERI1	ENST00000520684.5	c.109-8_109-7insGT		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5
ERI1	ENST00000521844.1	c.*197-8_*197-7insGT		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 136418 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0000291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000223 AC: 29 AN: 1298838 Hom.: 0 Cov.: 35 AF XY: 0.0000186 AC XY: 12 AN XY: 643526

Gnomad4 AFR exome AF: 0.0000377

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000471

Gnomad4 EAS exome AF: 0.0000283

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000227

Gnomad4 OTH exome AF: 0.0000568

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000147 AC: 2 AN: 136466 Hom.: 0 Cov.: 23 AF XY: 0.0000151 AC XY: 1 AN XY: 66030

Gnomad4 AFR AF: 0.0000291

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000539

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1585184680; hg19: chr8-8865471;