Variant rs34214100 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MCHR1	NM_005297.4 linkuse as main transcript	c.994G>A	p.Gly332Arg	missense_variant	2/2	ENST00000249016.5	NP_005288.4
LOC124905123	XR_007068110.1 linkuse as main transcript	n.189-1083C>T		intron_variant, non_coding_transcript_variant
LOC124905123	XR_007068109.1 linkuse as main transcript	n.3071C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MCHR1	ENST00000249016.5 linkuse as main transcript	c.994G>A	p.Gly332Arg	missense_variant	2/2	1	NM_005297.4	ENSP00000249016	P1
MCHR1	ENST00000381433.3 linkuse as main transcript	c.616G>A	p.Gly206Arg	missense_variant	3/3	1		ENSP00000370841
MCHR1	ENST00000498400.1 linkuse as main transcript	n.1044G>A		non_coding_transcript_exon_variant	2/2	1
	ENST00000688408.2 linkuse as main transcript	n.198-1083C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00124

AC XY:

167

AN XY:

135212

show subpopulations

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.:

Cov.:

AF XY:

0.000536

AC XY:

390

AN XY:

727084

show subpopulations

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:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74506

show subpopulations

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.:

Bravo

AF:

0.000835

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00129

AC:

157

Asia WGS

AF:

0.00346

AC:

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

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.069

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

0.95

D;D

PrimateAI

Uncertain

0.54

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over