21-46287125-TAAA-TAAAAAAA

Variant names:

• chr21-46287125-T-TAAAA
• rs58271568
• NM_001314025.2:c.210+9_210+12dupAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000397701.9(YBEY):​c.210+2_210+3insAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,477,522 control chromosomes in the GnomAD database, including 86 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 0)
  • Exomes 𝑓: 0.028 (86 hom.)
• Consequence: YBEY ENST00000397701.9 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890

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

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0278 (36879/1328070) while in subpopulation AMR AF= 0.0442 (1353/30600). AF 95% confidence interval is 0.0423. There are 86 homozygotes in gnomad4_exome. There are 18578 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 86 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2	c.210+9_210+12dupAAAA		intron_variant	Intron 2 of 4	ENST00000397701.9	NP_001300954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBEY	ENST00000397701.9	c.210+2_210+3insAAAA		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4

Frequencies

GnomAD3 genomes AF: 0.000415 AC: 62 AN: 149348 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000467

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000430

Gnomad OTH AF: 0.000487

GnomAD3 exomes AF: 0.0521 AC: 7088 AN: 136068 Hom.: 162 AF XY: 0.0529 AC XY: 3930 AN XY: 74236

Gnomad AFR exome AF: 0.0232

Gnomad AMR exome AF: 0.0690

Gnomad ASJ exome AF: 0.0654

Gnomad EAS exome AF: 0.0279

Gnomad SAS exome AF: 0.0414

Gnomad FIN exome AF: 0.0549

Gnomad NFE exome AF: 0.0578

Gnomad OTH exome AF: 0.0579

GnomAD4 exome AF: 0.0278 AC: 36879 AN: 1328070 Hom.: 86 Cov.: 31 AF XY: 0.0282 AC XY: 18578 AN XY: 658464

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0442

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.00913

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.0395

Gnomad4 NFE exome AF: 0.0282

Gnomad4 OTH exome AF: 0.0266

GnomAD4 genome AF: 0.000415 AC: 62 AN: 149452 Hom.: 0 Cov.: 0 AF XY: 0.000426 AC XY: 31 AN XY: 72734

Gnomad4 AFR AF: 0.0000490

Gnomad4 AMR AF: 0.000467

Gnomad4 ASJ AF: 0.000580

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00216

Gnomad4 NFE AF: 0.000430

Gnomad4 OTH AF: 0.000483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58271568; hg19: chr21-47707039;