NM_005297.4:c.-42A>C

Variant names:

• chr22-40679611-A-C
• rs146834583
• NM_005297.4:c.-42A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005297.4(MCHR1):​c.-42A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,454 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MCHR1 NM_005297.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 3 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08075163).

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.-42A>C		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.-42A>C		5_prime_UTR	Exon 1 of 2	ENSP00000249016.5	Q99705
	MCHR1	ENST00000381433.3	TSL:1	c.-42A>C		5_prime_UTR	Exon 1 of 3	ENSP00000370841.3	A6ZJ87
	MCHR1	ENST00000498400.1	TSL:1	n.132+207A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151804 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249580 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461650 Hom.: 0 Cov.: 64 AF XY: 0.00000413 AC XY: 3 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111856

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151804 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74142

African (AFR) AF: 0.00 AC: 0 AN: 41300

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67948

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	4.5
DANN	Benign	0.94
DEOGEN2	Benign	0.080	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.045
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	0.78	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.67		Gain of MoRF binding (P = 0.0134)
MVP		0.46
MPC		0.14
ClinPred		0.070	T
GERP RS		-0.75
PromoterAI		-0.056	Neutral
Varity_R		0.057
gMVP		0.42

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: rs146834583; hg19: chr22-41075615;