rs11914085

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005297.4(MCHR1):c.100G>A(p.Gly34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00651 in 1,614,002 control chromosomes in the GnomAD database, including 603 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 297 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 306 hom. )

Consequence

MCHR1
NM_005297.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:4

Conservation

PhyloP100: 0.0980

Publications

5 publications found

Variant links:

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]

MCHR1 links:

LOC124905123 (HGNC:):

LOC124905123 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018067956).

BP6

Variant 22-40680966-G-A is Benign according to our data. Variant chr22-40680966-G-A is described in ClinVar as [Benign]. Clinvar id is 1284474.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCHR1	NM_005297.4 link	c.100G>A	p.Gly34Arg	missense_variant	Exon 2 of 2	ENST00000249016.5	NP_005288.4	Q99705
LOC124905123	XR_007068109.1 link	n.3965C>T		non_coding_transcript_exon_variant	Exon 1 of 2
LOC124905123	XR_007068110.1 link	n.189-189C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCHR1	ENST00000249016.5 link	c.100G>A	p.Gly34Arg	missense_variant	Exon 2 of 2	1	NM_005297.4	ENSP00000249016.5		Q99705

Frequencies

GnomAD3 genomes

AF:

0.0339

AC:

5149

AN:

152040

Hom.:

295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.00882

AC:

2217

AN:

251270

AF XY:

0.00638

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00365

AC:

5342

AN:

1461844

Hom.:

306

Cov.:

AF XY:

0.00315

AC XY:

2289

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.130

AC:

4344

AN:

33472

American (AMR)

AF:

0.00472

AC:

211

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000243

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00416

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000249

AC:

277

AN:

1112010

Other (OTH)

AF:

0.00767

AC:

463

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

318

637

955

1274

1592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0339

AC:

5162

AN:

152158

Hom.:

297

Cov.:

AF XY:

0.0326

AC XY:

2423

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.118

AC:

4898

AN:

41468

American (AMR)

AF:

0.0124

AC:

190

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000367

AC:

AN:

68028

Other (OTH)

AF:

0.0223

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

221

441

662

882

1103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0129

Hom.:

219

Bravo

AF:

0.0386

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.121

AC:

534

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0113

AC:

1368

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

MCHR1-related disorder

Benign:1

Dec 29, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.2

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.097

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

N;.

PhyloP100

0.098

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.017

Sift

Benign

0.59

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0

B;.

Vest4

0.18

MutPred

0.11

Gain of glycosylation at P100 (P = 0.0791);Gain of glycosylation at P100 (P = 0.0791);

MPC

0.15

ClinPred

0.0028

GERP RS

1.6

Varity_R

0.044

gMVP

0.69

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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rs11914085

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over