6-84089072-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_138409.4(MRAP2):c.228-19A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,588,048 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (13 hom.)
• Consequence: MRAP2 NM_138409.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.48

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 6-84089072-A-C is Benign according to our data. Variant chr6-84089072-A-C is described in ClinVar as [Benign]. Clinvar id is 1601123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0068 (1035/152168) while in subpopulation AFR AF= 0.0221 (919/41528). AF 95% confidence interval is 0.0209. There are 14 homozygotes in gnomad4. There are 504 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1036 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRAP2	NM_138409.4	c.228-19A>C		intron_variant		ENST00000257776.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRAP2	ENST00000257776.5	c.228-19A>C		intron_variant		1	NM_138409.4	P1

Frequencies

GnomAD3 genomes AF: 0.00681 AC: 1036 AN: 152050 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00222 AC: 507 AN: 228200 Hom.: 7 AF XY: 0.00178 AC XY: 221 AN XY: 124022

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.00141

Gnomad ASJ exome AF: 0.00173

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000713

Gnomad FIN exome AF: 0.0000994

Gnomad NFE exome AF: 0.000727

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00124 AC: 1777 AN: 1435880 Hom.: 13 Cov.: 30 AF XY: 0.00116 AC XY: 827 AN XY: 712752

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00263

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000534

Gnomad4 FIN exome AF: 0.000153

Gnomad4 NFE exome AF: 0.000596

Gnomad4 OTH exome AF: 0.00249

GnomAD4 genome AF: 0.00680 AC: 1035 AN: 152168 Hom.: 14 Cov.: 32 AF XY: 0.00678 AC XY: 504 AN XY: 74382

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00530 Hom.: 1

Bravo AF: 0.00775

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 03, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.029
Dann	Benign	0.26

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: rs141426872; hg19: chr6-84798791;