6-99967676-G-C

Variant names:

• chr6-99967676-G-C
• rs9376618
• NM_001040179.2:c.-27-11502C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040179.2(MCHR2):​c.-27-11502C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,966 control chromosomes in the GnomAD database, including 7,691 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 0.29 (7691 hom., cov: 32)
• Consequence: MCHR2 NM_001040179.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCHR2	NM_001040179.2	c.-27-11502C>G		intron_variant	Intron 1 of 5	ENST00000281806.7	NP_001035269.1
MCHR2	NM_032503.3	c.-27-11502C>G		intron_variant	Intron 1 of 5		NP_115892.2
MCHR2	XM_024446571.2	c.-27-11502C>G		intron_variant	Intron 1 of 5		XP_024302339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCHR2	ENST00000281806.7	c.-27-11502C>G		intron_variant	Intron 1 of 5	2	NM_001040179.2	ENSP00000281806.2
MCHR2	ENST00000369212.2	c.-27-11502C>G		intron_variant	Intron 1 of 5	1		ENSP00000358214.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44740 AN: 151846 Hom.: 7692 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.294 AC: 44751 AN: 151966 Hom.: 7691 Cov.: 32 AF XY: 0.297 AC XY: 22062 AN XY: 74270

African (AFR) AF: 0.115 AC: 4785 AN: 41484

American (AMR) AF: 0.409 AC: 6250 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1367 AN: 3462

East Asian (EAS) AF: 0.125 AC: 645 AN: 5164

South Asian (SAS) AF: 0.356 AC: 1716 AN: 4814

European-Finnish (FIN) AF: 0.344 AC: 3624 AN: 10534

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25324 AN: 67932

Other (OTH) AF: 0.308 AC: 647 AN: 2102

Alfa AF: 0.209 Hom.: 498

Bravo AF: 0.288

Asia WGS AF: 0.248 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.40
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9376618; hg19: chr6-100415552;