Genetic Variant YBEY:c.210+7_210+12dupAAAAAA (chr21-46287125-T-TAAAAAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000397701.9(YBEY):c.210+2_210+3insAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,416,036 control chromosomes in the GnomAD database, including 9,645 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7179 hom., cov: 0)

Exomes 𝑓: 0.20 ( 2466 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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2 link	c.210+7_210+12dupAAAAAA		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+3insAAAAAA		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4		P58557-1

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

45683

AN:

148384

Hom.:

7174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.314

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.303

GnomAD2 exomes

AF:

0.129

AC:

17531

AN:

136068

AF XY:

0.126

show subpopulations

Gnomad AFR exome

AF:

0.0988

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.202

AC:

255865

AN:

1267564

Hom.:

2466

Cov.:

AF XY:

0.198

AC XY:

124393

AN XY:

626898

show subpopulations

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

African (AFR)

AF:

0.160

AC:

4407

AN:

27590

American (AMR)

AF:

0.197

AC:

5682

AN:

28838

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

4272

AN:

21158

East Asian (EAS)

AF:

0.144

AC:

4759

AN:

33082

South Asian (SAS)

AF:

0.158

AC:

10799

AN:

68288

European-Finnish (FIN)

AF:

0.169

AC:

7431

AN:

43876

Middle Eastern (MID)

AF:

0.161

AC:

752

AN:

4678

European-Non Finnish (NFE)

AF:

0.210

AC:

207613

AN:

988228

Other (OTH)

AF:

0.196

AC:

10150

AN:

51826

⚠️ 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: 0.369

Heterozygous variant carriers

11708

23416

35123

46831

58539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.308

AC:

45693

AN:

148472

Hom.:

7179

Cov.:

AF XY:

0.310

AC XY:

22356

AN XY:

72192

show subpopulations

African (AFR)

AF:

0.271

AC:

10980

AN:

40516

American (AMR)

AF:

0.382

AC:

5681

AN:

14880

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1222

AN:

3440

East Asian (EAS)

AF:

0.306

AC:

1552

AN:

5078

South Asian (SAS)

AF:

0.304

AC:

1427

AN:

4696

European-Finnish (FIN)

AF:

0.308

AC:

2915

AN:

9452

Middle Eastern (MID)

AF:

0.309

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.313

AC:

21027

AN:

67156

Other (OTH)

AF:

0.301

AC:

621

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

1361

2721

4082

5442

6803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.130

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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21-46287125-TAAA-TAAAAAAAAA

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