6-99984779-C-T

Variant names:

• chr6-99984779-C-T
• rs7754794
• NM_001040179.2:c.-28+9157G>A

Variant summary

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

The NM_001040179.2(MCHR2):​c.-28+9157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,850 control chromosomes in the GnomAD database, including 10,543 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 0.36 (10543 hom., cov: 31)
• Consequence: MCHR2 NM_001040179.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCHR2	NM_001040179.2	c.-28+9157G>A		intron_variant	Intron 1 of 5	ENST00000281806.7	NP_001035269.1
MCHR2	NM_032503.3	c.-28+9396G>A		intron_variant	Intron 1 of 5		NP_115892.2
MCHR2	XM_024446571.2	c.-28+8985G>A		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.-28+9157G>A		intron_variant	Intron 1 of 5	2	NM_001040179.2	ENSP00000281806.2
MCHR2	ENST00000369212.2	c.-28+9396G>A		intron_variant	Intron 1 of 5	1		ENSP00000358214.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55245 AN: 151730 Hom.: 10535 Cov.: 31

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.00926

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.364 AC: 55261 AN: 151850 Hom.: 10543 Cov.: 31 AF XY: 0.359 AC XY: 26612 AN XY: 74222

African (AFR) AF: 0.397 AC: 16433 AN: 41414

American (AMR) AF: 0.359 AC: 5481 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1302 AN: 3466

East Asian (EAS) AF: 0.00928 AC: 48 AN: 5170

South Asian (SAS) AF: 0.195 AC: 941 AN: 4822

European-Finnish (FIN) AF: 0.367 AC: 3876 AN: 10548

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25882 AN: 67856

Other (OTH) AF: 0.347 AC: 730 AN: 2102

Alfa AF: 0.342 Hom.: 4878

Bravo AF: 0.364

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.29
PhyloP100		0.21
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: rs7754794; hg19: chr6-100432655;