chr6-84097959-T-G

Position:

• chr6-84097959-T-G

Variant summary

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

The XM_017010221.3(MRAP2):​c.227+34967T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 152,244 control chromosomes in the GnomAD database, including 302 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 0.052 (302 hom., cov: 32)
• Consequence: MRAP2 XM_017010221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

Genes affected

MRAP2 (HGNC:21232): (melanocortin 2 receptor accessory protein 2) This gene encodes a protein that modulates melanocortin receptor signaling. The encoded protein has been shown to interact with all known melanocortin receptors and may regulate both receptor trafficking and activation in response to ligands. Mice lacking a functional copy of this gene exhibit severe obesity and a mutation in this gene may be associated with severe obesity in human patients. [provided by RefSeq, Oct 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRAP2	XM_017010221.3	c.227+34967T>G		intron_variant			XP_016865710.1
		n.84097959T>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7935 AN: 152126 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0521 AC: 7933 AN: 152244 Hom.: 302 Cov.: 32 AF XY: 0.0562 AC XY: 4184 AN XY: 74426

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0344

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.0398

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.0639

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0607 Hom.: 157

Bravo AF: 0.0422

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10485092; hg19: chr6-84807678;