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. The variant received -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
• Publications: 6 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001314025.2. 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+13T>A		intron	N/A	NP_001300954.1	P58557-1
	YBEY	NM_058181.3		c.210+13T>A		intron	N/A	NP_478061.1	P58557-1
	YBEY	NM_001314022.2		c.210+13T>A		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+13T>A		intron	N/A	ENSP00000380813.4	P58557-1
	YBEY	ENST00000329319.7	TSL:1	c.210+13T>A		intron	N/A	ENSP00000329614.3	P58557-1
	YBEY	ENST00000339195.10	TSL:1	c.210+13T>A		intron	N/A	ENSP00000340675.6	P58557-2

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

GnomAD2 exomes AF: 0.385 AC: 75237 AN: 195262 AF XY: 0.383

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 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

African (AFR) AF: 0.275 AC: 8589 AN: 31182

American (AMR) AF: 0.486 AC: 16191 AN: 33330

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 11186 AN: 24040

East Asian (EAS) AF: 0.254 AC: 9892 AN: 38872

South Asian (SAS) AF: 0.347 AC: 27529 AN: 79354

European-Finnish (FIN) AF: 0.464 AC: 23290 AN: 50180

Middle Eastern (MID) AF: 0.367 AC: 1900 AN: 5172

European-Non Finnish (NFE) AF: 0.460 AC: 495221 AN: 1077478

Other (OTH) AF: 0.432 AC: 24987 AN: 57882

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

African (AFR) AF: 0.301 AC: 12347 AN: 41038

American (AMR) AF: 0.470 AC: 7095 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1605 AN: 3446

East Asian (EAS) AF: 0.310 AC: 1590 AN: 5126

South Asian (SAS) AF: 0.355 AC: 1695 AN: 4780

European-Finnish (FIN) AF: 0.471 AC: 4720 AN: 10014

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 30764 AN: 67536

Other (OTH) AF: 0.392 AC: 817 AN: 2086

Alfa AF: 0.0888 Hom.: 411

Bravo AF: 0.404

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.80
DANN	Benign	0.19
PhyloP100		-0.0070
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61182475; hg19: chr21-47707050; COSMIC: COSV107340562; COSMIC: COSV107340562;