21-32302884-A-G

Variant names:

• chr21-32302884-A-G
• rs9975800
• NM_001379228.1:c.107-3756A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379228.1(MRAP):​c.107-3756A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,126 control chromosomes in the GnomAD database, including 50,538 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 0.81 (50538 hom., cov: 31)
• Consequence: MRAP NM_001379228.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 2 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]

MRAP-AS1 (HGNC:40108): (MRAP antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.857 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAP	NM_001379228.1	MANE Select	c.107-3756A>G		intron	N/A	NP_001366157.1
	MRAP	NM_178817.4		c.107-3756A>G		intron	N/A	NP_848932.1
	MRAP	NM_001285394.2		c.-71-3756A>G		intron	N/A	NP_001272323.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAP	ENST00000303645.10	TSL:1 MANE Select	c.107-3756A>G		intron	N/A	ENSP00000306697.5
	MRAP	ENST00000399784.6	TSL:1	c.107-3756A>G		intron	N/A	ENSP00000382684.2
	MRAP	ENST00000339944.4	TSL:1	c.107-3756A>G		intron	N/A	ENSP00000343661.4

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123434 AN: 152008 Hom.: 50486 Cov.: 31

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.817

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.812 AC: 123542 AN: 152126 Hom.: 50538 Cov.: 31 AF XY: 0.809 AC XY: 60167 AN XY: 74346

African (AFR) AF: 0.744 AC: 30828 AN: 41462

American (AMR) AF: 0.820 AC: 12531 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2955 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3277 AN: 5166

South Asian (SAS) AF: 0.752 AC: 3625 AN: 4820

European-Finnish (FIN) AF: 0.831 AC: 8795 AN: 10580

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58702 AN: 68016

Other (OTH) AF: 0.818 AC: 1729 AN: 2114

Alfa AF: 0.846 Hom.: 212398

Bravo AF: 0.806

Asia WGS AF: 0.684 AC: 2376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.41
PhyloP100		-0.24
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: rs9975800; hg19: chr21-33675195;