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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new If you want to explore the variant's impact on the transcript ENST00000397701.9, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397701.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YBEY	NM_001314025.2	MANE Select	c.210+6_210+12dupAAAAAAA	intron	N/A	NP_001300954.1	P58557-1
YBEY	NM_058181.3		c.210+6_210+12dupAAAAAAA	intron	N/A	NP_478061.1	P58557-1
YBEY	NM_001314022.2		c.210+6_210+12dupAAAAAAA	intron	N/A	NP_001300951.1	P58557-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YBEY	ENST00000397701.9	TSL:2 MANE Select	c.210+2_210+3insAAAAAAA	splice_region intron	N/A	ENSP00000380813.4	P58557-1
YBEY	ENST00000329319.7	TSL:1	c.210+2_210+3insAAAAAAA	splice_region intron	N/A	ENSP00000329614.3	P58557-1
YBEY	ENST00000339195.10	TSL:1	c.210+2_210+3insAAAAAAA	splice_region intron	N/A	ENSP00000340675.6	P58557-2

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), 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

Age Distribution

Exome Het

Exome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00428

Hom.:

259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over