rs34214100

chr22-40681860-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005297.4(MCHR1):c.994G>A(p.Gly332Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000557 in 1,613,814 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00061 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (13 hom.)
• Consequence: MCHR1 NM_005297.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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=0.004900515).
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000551 (806/1461472) while in subpopulation EAS AF= 0.0193 (768/39700). AF 95% confidence interval is 0.0182. There are 13 homozygotes in gnomad4_exome. There are 390 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCHR1	NM_005297.4	c.994G>A	p.Gly332Arg	missense_variant	2/2	ENST00000249016.5
LOC124905123	XR_007068110.1	n.189-1083C>T		intron_variant, non_coding_transcript_variant
LOC124905123	XR_007068109.1	n.3071C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCHR1	ENST00000249016.5	c.994G>A	p.Gly332Arg	missense_variant	2/2	1	NM_005297.4	P1
MCHR1	ENST00000381433.3	c.616G>A	p.Gly206Arg	missense_variant	3/3	1
MCHR1	ENST00000498400.1	n.1044G>A		non_coding_transcript_exon_variant	2/2	1
	ENST00000688408.2	n.198-1083C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152224 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00138 AC: 345 AN: 249614 Hom.: 5 AF XY: 0.00124 AC XY: 167 AN XY: 135212

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0185

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000551 AC: 806 AN: 1461472 Hom.: 13 Cov.: 32 AF XY: 0.000536 AC XY: 390 AN XY: 727084

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0193

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.000414

GnomAD4 genome AF: 0.000610 AC: 93 AN: 152342 Hom.: 3 Cov.: 32 AF XY: 0.000725 AC XY: 54 AN XY: 74506

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000359 Hom.: 0

Bravo AF: 0.000835

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00129 AC: 157

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.043	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.79	T;T
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.99	N;N
REVEL	Benign	0.17
Sift	Benign	0.20	T;T
Sift4G	Uncertain	0.013	D;D
Polyphen		0.42	B;.
Vest4		0.13
MutPred		0.40		Gain of MoRF binding (P = 0.0171);.;
MVP		0.78
MPC		0.16
ClinPred		0.030	T
GERP RS		5.4
Varity_R		0.12
gMVP		0.34

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: rs34214100; hg19: chr22-41077864;