rs10499026

Positions:

• chr6-99949650-G-A

Variant summary

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

The NM_001040179.2(MCHR2):​c.183-1679C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,984 control chromosomes in the GnomAD database, including 2,325 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 0.17 (2325 hom., cov: 32)
• Consequence: MCHR2 NM_001040179.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

Genes affected

MCHR2 (HGNC:20867): (melanin concentrating hormone receptor 2) Predicted to enable G protein-coupled peptide receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCHR2	NM_001040179.2	c.183-1679C>T		intron_variant		ENST00000281806.7
MCHR2	NM_032503.3	c.183-1679C>T		intron_variant
MCHR2	XM_024446571.2	c.183-1679C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCHR2	ENST00000281806.7	c.183-1679C>T		intron_variant		2	NM_001040179.2	P1
MCHR2	ENST00000369212.2	c.183-1679C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25578 AN: 151866 Hom.: 2325 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.168 AC: 25597 AN: 151984 Hom.: 2325 Cov.: 32 AF XY: 0.165 AC XY: 12239 AN XY: 74290

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.0944

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.174

Alfa AF: 0.171 Hom.: 3770

Bravo AF: 0.165

Asia WGS AF: 0.0510 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.65

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: rs10499026; hg19: chr6-100397526;