rs2236611

chr21-32312969-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014825.3(URB1):c.*1949G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,090 control chromosomes in the GnomAD database, including 27,605 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (27598 hom., cov: 33)
  • Exomes 𝑓: 0.85 (7 hom.)
• Consequence: URB1 NM_014825.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

Genes affected

URB1 (HGNC:17344): (URB1 ribosome biogenesis homolog) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

MRAP (HGNC:1304): (melanocortin 2 receptor accessory protein) This gene encodes a melanocortin receptor-interacting protein. The encoded protein regulates trafficking and function of the melanocortin 2 receptor in the adrenal gland. The encoded protein can also modulate signaling of other melanocortin receptors. Mutations in this gene have been associated with familial glucocorticoid deficiency type 2. Alternatively spliced transcript variants have been described. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
URB1	NM_014825.3	c.*1949G>A		3_prime_UTR_variant	39/39	ENST00000382751.4
MRAP	NM_206898.2	c.207-1582C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
URB1	ENST00000382751.4	c.*1949G>A		3_prime_UTR_variant	39/39	1	NM_014825.3	P1
MRAP	ENST00000339944.4	c.207-1582C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82924 AN: 151950 Hom.: 27605 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.850 AC: 17 AN: 20 Hom.: 7 Cov.: 0 AF XY: 0.850 AC XY: 17 AN XY: 20

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.545 AC: 82912 AN: 152070 Hom.: 27598 Cov.: 33 AF XY: 0.544 AC XY: 40434 AN XY: 74316

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.555

Alfa AF: 0.685 Hom.: 37517

Bravo AF: 0.507

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.58
Dann	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2236611; hg19: chr21-33685280;