Variant 6-84055452-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_138409.4(MRAP2):c.127+7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,609,802 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 16 hom., cov: 32)

Exomes 𝑓: 0.015 ( 214 hom. )

Consequence

MRAP2
NM_138409.4 splice_region, intron

Scores

Splicing: ADA: 0.0001131

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.759

Variant links:

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]

MRAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 6-84055452-T-G is Benign according to our data. Variant chr6-84055452-T-G is described in ClinVar as [Benign]. Clinvar id is 1570255.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-84055452-T-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0111 (1693/152316) while in subpopulation SAS AF= 0.022 (106/4824). AF 95% confidence interval is 0.0186. There are 16 homozygotes in gnomad4. There are 823 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1693 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRAP2	NM_138409.4 linkuse as main transcript	c.127+7T>G		splice_region_variant, intron_variant		ENST00000257776.5	NP_612418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRAP2	ENST00000257776.5 linkuse as main transcript	c.127+7T>G		splice_region_variant, intron_variant		1	NM_138409.4	ENSP00000257776	P1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1691

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0217

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0140

AC:

3480

AN:

248002

Hom.:

AF XY:

0.0151

AC XY:

2028

AN XY:

134110

show subpopulations

Gnomad AFR exome

AF:

0.00242

Gnomad AMR exome

AF:

0.00832

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0237

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0150

AC:

21799

AN:

1457486

Hom.:

214

Cov.:

AF XY:

0.0154

AC XY:

11175

AN XY:

725080

show subpopulations

Gnomad4 AFR exome

AF:

0.00229

Gnomad4 AMR exome

AF:

0.00859

Gnomad4 ASJ exome

AF:

0.0399

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0243

Gnomad4 FIN exome

AF:

0.00947

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.0111

AC:

1693

AN:

152316

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

823

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0220

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.0143

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0144

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0159

EpiControl

AF:

0.0170

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MRAP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.83

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over