Genetic Variant YBEY:c.210+9_210+12dupAAAA (chr21-46287125-T-TAAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000397701.9(YBEY):c.210+2_210+3insAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,477,522 control chromosomes in the GnomAD database, including 86 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 0)

Exomes 𝑓: 0.028 ( 86 hom. )

Consequence

YBEY
ENST00000397701.9 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.890

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 86 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2 link	c.210+9_210+12dupAAAA		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+3insAAAA		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4		P58557-1

Frequencies

GnomAD3 genomes

AF:

0.000415

AC:

AN:

149348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000467

Gnomad ASJ

AF:

0.000580

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000430

Gnomad OTH

AF:

0.000487

GnomAD2 exomes

AF:

0.0521

AC:

7088

AN:

136068

AF XY:

0.0529

show subpopulations

Gnomad AFR exome

AF:

0.0232

Gnomad AMR exome

AF:

0.0690

Gnomad ASJ exome

AF:

0.0654

Gnomad EAS exome

AF:

0.0279

Gnomad FIN exome

AF:

0.0549

Gnomad NFE exome

AF:

0.0578

Gnomad OTH exome

AF:

0.0579

GnomAD4 exome

AF:

0.0278

AC:

36879

AN:

1328070

Hom.:

Cov.:

AF XY:

0.0282

AC XY:

18578

AN XY:

658464

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0107

AC:

314

AN:

29224

American (AMR)

AF:

0.0442

AC:

1353

AN:

30600

Ashkenazi Jewish (ASJ)

AF:

0.0359

AC:

809

AN:

22524

East Asian (EAS)

AF:

0.00913

AC:

328

AN:

35922

South Asian (SAS)

AF:

0.0221

AC:

1641

AN:

74206

European-Finnish (FIN)

AF:

0.0395

AC:

1865

AN:

47246

Middle Eastern (MID)

AF:

0.0226

AC:

112

AN:

4954

European-Non Finnish (NFE)

AF:

0.0282

AC:

29000

AN:

1028684

Other (OTH)

AF:

0.0266

AC:

1457

AN:

54710

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.299

Heterozygous variant carriers

2666

5331

7997

10662

13328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000415

AC:

AN:

149452

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

AN XY:

72734

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000490

AC:

AN:

40800

American (AMR)

AF:

0.000467

AC:

AN:

15000

Ashkenazi Jewish (ASJ)

AF:

0.000580

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.00216

AC:

AN:

9702

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000430

AC:

AN:

67378

Other (OTH)

AF:

0.000483

AC:

AN:

2072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.356

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0213

Hom.:

259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.89

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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chr21-46287125-T-TAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over