rs2236611

Variant names:

• chr21-32312969-C-T
• rs2236611
• NM_014825.3:c.*1949G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

MRAP Gene-Disease associations (from GenCC):

• glucocorticoid deficiency 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• familial glucocorticoid deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014825.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	URB1	NM_014825.3	MANE Select	c.*1949G>A		3_prime_UTR	Exon 39 of 39	NP_055640.2
	MRAP	NM_206898.2		c.207-1582C>T		intron	N/A	NP_996781.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	URB1	ENST00000382751.4	TSL:1 MANE Select	c.*1949G>A		3_prime_UTR	Exon 39 of 39	ENSP00000372199.3
	MRAP	ENST00000339944.4	TSL:1	c.207-1582C>T		intron	N/A	ENSP00000343661.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.917 AC: 11 AN: 12

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.166 AC: 6891 AN: 41464

American (AMR) AF: 0.514 AC: 7851 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2389 AN: 3472

East Asian (EAS) AF: 0.419 AC: 2164 AN: 5164

South Asian (SAS) AF: 0.588 AC: 2833 AN: 4814

European-Finnish (FIN) AF: 0.746 AC: 7884 AN: 10568

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50888 AN: 67984

Other (OTH) AF: 0.555 AC: 1174 AN: 2114

Alfa AF: 0.656 Hom.: 99047

Bravo AF: 0.507

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.56
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236611; hg19: chr21-33685280;