Genetic Variant YBEY:c.210+8_210+12dupAAAAA (chr21-46287125-T-TAAAAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000397701.9(YBEY):c.210+2_210+3insAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,427,076 control chromosomes in the GnomAD database, including 2,261 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.094 ( 856 hom., cov: 0)

Exomes 𝑓: 0.15 ( 1405 hom. )

Consequence

YBEY
ENST00000397701.9 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.890

Variant links:

Genes affected

YBEY (HGNC:1299): (ybeY metalloendoribonuclease) This gene encodes a highly conserved metalloprotein. A similar protein in bacteria acts as an endoribonuclease, and is thought to function in ribosomal RNA maturation and ribosome assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

YBEY links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 21-46287125-T-TAAAAA is Benign according to our data. Variant chr21-46287125-T-TAAAAA is described in ClinVar as [Benign]. Clinvar id is 403076.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2 link	c.210+8_210+12dupAAAAA		intron_variant	Intron 2 of 4	ENST00000397701.9	NP_001300954.1	P58557-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBEY	ENST00000397701.9 link	c.210+2_210+3insAAAAA		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4		P58557-1

Frequencies

GnomAD3 genomes

AF:

0.0939

AC:

14006

AN:

149096

Hom.:

857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.0760

Gnomad AMR

AF:

0.0824

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.000975

Gnomad SAS

AF:

0.0470

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0962

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.0875

GnomAD3 exomes

AF:

0.136

AC:

18450

AN:

136068

Hom.:

506

AF XY:

0.136

AC XY:

10063

AN XY:

74236

show subpopulations

Gnomad AFR exome

AF:

0.0763

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.0713

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.147

AC:

187760

AN:

1277876

Hom.:

1405

Cov.:

AF XY:

0.145

AC XY:

91548

AN XY:

632296

show subpopulations

Gnomad4 AFR exome

AF:

0.0556

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.0412

Gnomad4 SAS exome

AF:

0.0886

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.158

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.0939

AC:

14010

AN:

149200

Hom.:

856

Cov.:

AF XY:

0.0917

AC XY:

6658

AN XY:

72580

show subpopulations

Gnomad4 AFR

AF:

0.0273

Gnomad4 AMR

AF:

0.0822

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.000978

Gnomad4 SAS

AF:

0.0473

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.0866

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

21-46287125-TAAA-TAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over