rs9975800

Positions:

• chr21-32302884-A-G
• chr21-32302884-A-T
• chr21-32302884-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRAP	NM_001379228.1	c.107-3756A>G		intron_variant		ENST00000303645.10	NP_001366157.1
MRAP	NM_001285394.2	c.-71-3756A>G		intron_variant			NP_001272323.1
MRAP	NM_178817.4	c.107-3756A>G		intron_variant			NP_848932.1
MRAP	NM_206898.2	c.107-3756A>G		intron_variant			NP_996781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRAP	ENST00000303645.10	c.107-3756A>G		intron_variant		1	NM_001379228.1	ENSP00000306697	P1
MRAP	ENST00000339944.4	c.107-3756A>G		intron_variant		1		ENSP00000343661
MRAP	ENST00000399784.6	c.107-3756A>G		intron_variant		1		ENSP00000382684	P1
MRAP	ENST00000497833.1	n.178-3756A>G		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.818

Alfa AF: 0.853 Hom.: 93448

Bravo AF: 0.806

Asia WGS AF: 0.684 AC: 2376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.41

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: rs9975800; hg19: chr21-33675195;