Genetic Variant YBEY:c.210+11_210+12dupAA (chr21-46287125-T-TAA) – 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+3insAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,506,712 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00057 ( 3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2 link	c.210+11_210+12dupAA		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+3insAA		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4		P58557-1

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149394

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000290

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

GnomAD2 exomes

AF:

0.00298

AC:

406

AN:

136068

AF XY:

0.00325

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.00400

Gnomad ASJ exome

AF:

0.00615

Gnomad EAS exome

AF:

0.00130

Gnomad FIN exome

AF:

0.00265

Gnomad NFE exome

AF:

0.00309

Gnomad OTH exome

AF:

0.00368

GnomAD4 exome

AF:

0.000567

AC:

769

AN:

1357318

Hom.:

Cov.:

AF XY:

0.000609

AC XY:

410

AN XY:

672834

show subpopulations

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

African (AFR)

AF:

0.000338

AC:

AN:

29600

American (AMR)

AF:

0.00159

AC:

AN:

31526

Ashkenazi Jewish (ASJ)

AF:

0.00138

AC:

AN:

23144

East Asian (EAS)

AF:

0.000192

AC:

AN:

36380

South Asian (SAS)

AF:

0.000740

AC:

AN:

75680

European-Finnish (FIN)

AF:

0.000780

AC:

AN:

48690

Middle Eastern (MID)

AF:

0.000397

AC:

AN:

5042

European-Non Finnish (NFE)

AF:

0.000523

AC:

550

AN:

1051290

Other (OTH)

AF:

0.000429

AC:

AN:

55966

⚠️ 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: 0.279

Heterozygous variant carriers

146

220

293

366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72630

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

40688

American (AMR)

AF:

0.00

AC:

AN:

14992

Ashkenazi Jewish (ASJ)

AF:

0.000290

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67392

Other (OTH)

AF:

0.00

AC:

AN:

2052

⚠️ 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: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00185

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

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr21-46287125-T-TAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over