rs61182475

Variant names:

• chr21-46287136-T-A
• rs61182475
• NM_001314025.2:c.210+13T>A

Your query was ambiguous. Multiple possible variants found:

• chr21-46287136-T-A
• chr21-46287136-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001314025.2(YBEY):​c.210+13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,547,800 control chromosomes in the GnomAD database, including 155,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12944 hom., cov: 30)
  • Exomes 𝑓: 0.44 (142151 hom.)
• Consequence: YBEY NM_001314025.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00700

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 21-46287136-T-A is Benign according to our data. Variant chr21-46287136-T-A is described in ClinVar as [Benign]. Clinvar id is 403614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2	c.210+13T>A		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+13T>A		intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4

Frequencies

GnomAD3 genomes AF: 0.406 AC: 60977 AN: 150198 Hom.: 12937 Cov.: 30

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.394

GnomAD3 exomes AF: 0.385 AC: 75237 AN: 195262 Hom.: 17263 AF XY: 0.383 AC XY: 40910 AN XY: 106768

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.474

Gnomad ASJ exome AF: 0.420

Gnomad EAS exome AF: 0.261

Gnomad SAS exome AF: 0.307

Gnomad FIN exome AF: 0.441

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.404

GnomAD4 exome AF: 0.443 AC: 618785 AN: 1397490 Hom.: 142151 Cov.: 31 AF XY: 0.439 AC XY: 304665 AN XY: 693860

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.465

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.406 AC: 61002 AN: 150310 Hom.: 12944 Cov.: 30 AF XY: 0.406 AC XY: 29797 AN XY: 73306

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.392

Alfa AF: 0.0888 Hom.: 411

Bravo AF: 0.404

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.80
DANN	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs61182475; hg19: chr21-47707050;