21-46287125-TAAA-TAAAAAAAAA

Variant names:

• chr21-46287125-T-TAAAAAA
• rs58271568
• NM_001314025.2:c.210+7_210+12dupAAAAAA

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890
• Publications: 1 publications found

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]

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBEY	NM_001314025.2	MANE Select	c.210+7_210+12dupAAAAAA		intron	N/A	NP_001300954.1	P58557-1
	YBEY	NM_058181.3		c.210+7_210+12dupAAAAAA		intron	N/A	NP_478061.1	P58557-1
	YBEY	NM_001314022.2		c.210+7_210+12dupAAAAAA		intron	N/A	NP_001300951.1	P58557-2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.308 AC: 45683 AN: 148384 Hom.: 7174 Cov.: 0

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

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.: 31 AF XY: 0.198 AC XY: 124393 AN XY: 626898

⚠️ 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), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.308 AC: 45693 AN: 148472 Hom.: 7179 Cov.: 0 AF XY: 0.310 AC XY: 22356 AN XY: 72192

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: 89 AN: 288

European-Non Finnish (NFE) AF: 0.313 AC: 21027 AN: 67156

Other (OTH) AF: 0.301 AC: 621 AN: 2064

Alfa AF: 0.130 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 (auto)

Splicing

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

Other links and lift over

dbSNP: rs58271568; hg19: chr21-47707039; COSMIC: COSV52439575; COSMIC: COSV52439575;