rs133072

Positions:

• chr22-40679539-A-G
• chr22-40679539-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCHR1	NM_005297.4	c.-114A>G		5_prime_UTR_variant	1/2	ENST00000249016.5
LOC124905123	XR_007068110.1	n.358+1069T>C		intron_variant, non_coding_transcript_variant
LOC124905123	XR_007068109.1	n.4323+1069T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCHR1	ENST00000249016.5	c.-114A>G		5_prime_UTR_variant	1/2	1	NM_005297.4	P1
MCHR1	ENST00000381433.3	c.-114A>G		5_prime_UTR_variant	1/3	1
MCHR1	ENST00000498400.1	n.132+135A>G		intron_variant, non_coding_transcript_variant		1
	ENST00000688408.2	n.367+1069T>C		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.616 AC: 153741 AN: 249508 Hom.: 50499 AF XY: 0.617 AC XY: 83355 AN XY: 135176

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 SAS exome AF: 0.471

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

Gnomad4 AFR exome AF: 0.697

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.990

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.697

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.632

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

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.638

Alfa AF: 0.637 Hom.: 66711

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 v4.3

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;T
MetaRNN	Benign	8.0e-7	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.070	N;N
REVEL	Benign	0.10
Sift	Benign	1.0	T;T
Sift4G	Benign	0.81	T;T
Polyphen		0.0	B;.
Vest4		0.060
MPC		0.14
ClinPred		0.0014	T
GERP RS		2.0
Varity_R		0.051
gMVP		0.24

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: rs133072; hg19: chr22-41075543; COSMIC: COSV50760293; COSMIC: COSV50760293;