chr21-32311867-C-G

Variant names:

• chr21-32311867-C-G
• rs17855143
• NM_001379228.1:c.390C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001379228.1(MRAP):​c.390C>G​(p.Thr130Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0075 in 1,614,154 control chromosomes in the GnomAD database, including 464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (34 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (430 hom.)
• Consequence: MRAP NM_001379228.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.280
• Publications: 4 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 21-32311867-C-G is Benign according to our data. Variant chr21-32311867-C-G is described in ClinVar as Benign. ClinVar VariationId is 339683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379228.1. 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
	MRAP	NM_001379228.1	MANE Select	c.390C>G	p.Thr130Thr	synonymous	Exon 3 of 3	NP_001366157.1	Q8TCY5-4
	URB1	NM_014825.3	MANE Select	c.*3051G>C		3_prime_UTR	Exon 39 of 39	NP_055640.2
	MRAP	NM_178817.4		c.390C>G	p.Thr130Thr	synonymous	Exon 5 of 5	NP_848932.1	Q8TCY5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAP	ENST00000303645.10	TSL:1 MANE Select	c.390C>G	p.Thr130Thr	synonymous	Exon 3 of 3	ENSP00000306697.5	Q8TCY5-4
	MRAP	ENST00000399784.6	TSL:1	c.390C>G	p.Thr130Thr	synonymous	Exon 5 of 5	ENSP00000382684.2	Q8TCY5-4
	URB1	ENST00000382751.4	TSL:1 MANE Select	c.*3051G>C		3_prime_UTR	Exon 39 of 39	ENSP00000372199.3	O60287

Frequencies

GnomAD3 genomes AF: 0.00727 AC: 1106 AN: 152224 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.0155 AC: 3863 AN: 249008 AF XY: 0.0172

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.0842

Gnomad FIN exome AF: 0.0202

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.00751 AC: 10984 AN: 1461812 Hom.: 430 Cov.: 31 AF XY: 0.00891 AC XY: 6483 AN XY: 727218

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 48 AN: 26136

East Asian (EAS) AF: 0.102 AC: 4058 AN: 39700

South Asian (SAS) AF: 0.0521 AC: 4497 AN: 86258

European-Finnish (FIN) AF: 0.0203 AC: 1083 AN: 53344

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.000639 AC: 711 AN: 1112010

Other (OTH) AF: 0.00873 AC: 527 AN: 60392

GnomAD4 genome AF: 0.00737 AC: 1122 AN: 152342 Hom.: 34 Cov.: 32 AF XY: 0.00912 AC XY: 679 AN XY: 74490

African (AFR) AF: 0.000818 AC: 34 AN: 41590

American (AMR) AF: 0.00111 AC: 17 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.0880 AC: 455 AN: 5172

South Asian (SAS) AF: 0.0593 AC: 286 AN: 4826

European-Finnish (FIN) AF: 0.0200 AC: 213 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00112 AC: 76 AN: 68020

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.00179 Hom.: 1

Bravo AF: 0.00471

Asia WGS AF: 0.0900 AC: 313 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Glucocorticoid deficiency 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs17855143; hg19: chr21-33684178; COSMIC: COSV57936716; COSMIC: COSV57936716;