22-40679539-A-G

Variant names:

• chr22-40679539-A-G
• rs133072
• NM_005297.4:c.-114A>G

Variant summary

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

The NM_005297.4(MCHR1):​c.-114A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,613,584 control chromosomes in the GnomAD database, including 326,880 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 0.65 (32867 hom., cov: 32)
  • Exomes 𝑓: 0.63 (294013 hom.)
• Consequence: MCHR1 NM_005297.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 33 publications found

Genes affected

MCHR1 (HGNC:4479): (melanin concentrating hormone receptor 1) The protein encoded by this gene, a member of the G protein-coupled receptor family 1, is an integral plasma membrane protein which binds melanin-concentrating hormone. The encoded protein can inhibit cAMP accumulation and stimulate intracellular calcium flux, and is probably involved in the neuronal regulation of food consumption. Although structurally similar to somatostatin receptors, this protein does not seem to bind somatostatin. [provided by RefSeq, Jul 2008]

ENSG00000289292 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.01129E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005297.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCHR1	NM_005297.4	MANE Select	c.-114A>G		5_prime_UTR	Exon 1 of 2	NP_005288.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCHR1	ENST00000249016.5	TSL:1 MANE Select	c.-114A>G		5_prime_UTR	Exon 1 of 2	ENSP00000249016.5	Q99705
	MCHR1	ENST00000381433.3	TSL:1	c.-114A>G		5_prime_UTR	Exon 1 of 3	ENSP00000370841.3	A6ZJ87
	MCHR1	ENST00000498400.1	TSL:1	n.132+135A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98872 AN: 151976 Hom.: 32835 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.616 AC: 153741 AN: 249508 AF XY: 0.617

Gnomad AFR exome AF: 0.696

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.629

Gnomad EAS exome AF: 0.982

Gnomad FIN exome AF: 0.700

Gnomad NFE exome AF: 0.646

Gnomad OTH exome AF: 0.608

GnomAD4 exome AF: 0.627 AC: 916910 AN: 1461490 Hom.: 294013 Cov.: 57 AF XY: 0.625 AC XY: 454442 AN XY: 727058

African (AFR) AF: 0.697 AC: 23339 AN: 33478

American (AMR) AF: 0.382 AC: 17085 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 16281 AN: 26134

East Asian (EAS) AF: 0.990 AC: 39298 AN: 39698

South Asian (SAS) AF: 0.473 AC: 40808 AN: 86252

European-Finnish (FIN) AF: 0.697 AC: 37130 AN: 53298

Middle Eastern (MID) AF: 0.618 AC: 3563 AN: 5766

European-Non Finnish (NFE) AF: 0.631 AC: 701252 AN: 1111796

Other (OTH) AF: 0.632 AC: 38154 AN: 60370

GnomAD4 genome AF: 0.651 AC: 98946 AN: 152094 Hom.: 32867 Cov.: 32 AF XY: 0.650 AC XY: 48336 AN XY: 74378

African (AFR) AF: 0.697 AC: 28888 AN: 41466

American (AMR) AF: 0.503 AC: 7681 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2199 AN: 3472

East Asian (EAS) AF: 0.978 AC: 5052 AN: 5166

South Asian (SAS) AF: 0.483 AC: 2329 AN: 4820

European-Finnish (FIN) AF: 0.693 AC: 7346 AN: 10602

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43361 AN: 67968

Other (OTH) AF: 0.638 AC: 1348 AN: 2114

Alfa AF: 0.639 Hom.: 100925

Bravo AF: 0.640

TwinsUK AF: 0.626 AC: 2320

ALSPAC AF: 0.632 AC: 2436

ESP6500AA AF: 0.690 AC: 3040

ESP6500EA AF: 0.636 AC: 5469

ExAC AF: 0.625 AC: 75872

Asia WGS AF: 0.716 AC: 2485 AN: 3478

EpiCase AF: 0.633

EpiControl AF: 0.644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.65
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	8.0e-7	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	N
PhyloP100		2.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.060
MPC		0.14
ClinPred		0.0014	T
GERP RS		2.0
PromoterAI		0.018	Neutral
Varity_R		0.051
gMVP		0.24
Mutation Taster		=95/5	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: rs133072; hg19: chr22-41075543; COSMIC: COSV50760293; COSMIC: COSV50760293;