Genetic Variant YBEY:c.210+6_210+12dupAAAAAAA (chr21-46287125-T-TAAAAAAA) – 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+3insAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0036 in 1,504,704 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 0.00087 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0039 ( 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:

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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 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2 link	c.210+6_210+12dupAAAAAAA		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+3insAAAAAAA		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4		P58557-1

Frequencies

GnomAD3 genomes

AF:

0.000870

AC:

130

AN:

149384

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000400

Gnomad ASJ

AF:

0.000871

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000309

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000712

Gnomad OTH

AF:

0.000976

GnomAD2 exomes

AF:

0.00570

AC:

776

AN:

136068

AF XY:

0.00583

show subpopulations

Gnomad AFR exome

AF:

0.00506

Gnomad AMR exome

AF:

0.00774

Gnomad ASJ exome

AF:

0.00692

Gnomad EAS exome

AF:

0.00564

Gnomad FIN exome

AF:

0.00578

Gnomad NFE exome

AF:

0.00543

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00390

AC:

5288

AN:

1355216

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

2485

AN XY:

671742

show subpopulations

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

African (AFR)

AF:

0.00335

AC:

AN:

29516

American (AMR)

AF:

0.00433

AC:

136

AN:

31406

Ashkenazi Jewish (ASJ)

AF:

0.00290

AC:

AN:

23098

East Asian (EAS)

AF:

0.00176

AC:

AN:

36306

South Asian (SAS)

AF:

0.00285

AC:

215

AN:

75454

European-Finnish (FIN)

AF:

0.00257

AC:

125

AN:

48558

Middle Eastern (MID)

AF:

0.00397

AC:

AN:

5040

European-Non Finnish (NFE)

AF:

0.00417

AC:

4374

AN:

1049984

Other (OTH)

AF:

0.00337

AC:

188

AN:

55854

⚠️ 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: 0.290

Heterozygous variant carriers

399

799

1198

1598

1997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000870

AC:

130

AN:

149488

Hom.:

Cov.:

AF XY:

0.000674

AC XY:

AN XY:

72740

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

40802

American (AMR)

AF:

0.000400

AC:

AN:

15010

Ashkenazi Jewish (ASJ)

AF:

0.000871

AC:

AN:

3446

East Asian (EAS)

AF:

0.000391

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.000309

AC:

AN:

9724

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000712

AC:

AN:

67382

Other (OTH)

AF:

0.000966

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00428

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

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21-46287125-TAAA-TAAAAAAAAAA

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