Variant 22-40679539-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	#exon/exons	MANE	Protein
MCHR1	NM_005297.4 linkuse as main transcript	c.-114A>G	5_prime_UTR_variant	1/2	ENST00000249016.5	NP_005288.4
LOC124905123	XR_007068110.1 linkuse as main transcript	n.358+1069T>C	intron_variant, non_coding_transcript_variant
LOC124905123	XR_007068109.1 linkuse as main transcript	n.4323+1069T>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
MCHR1	ENST00000249016.5 linkuse as main transcript	c.-114A>G	5_prime_UTR_variant	1/2	1	NM_005297.4	ENSP00000249016	P1
MCHR1	ENST00000381433.3 linkuse as main transcript	c.-114A>G	5_prime_UTR_variant	1/3	1		ENSP00000370841
MCHR1	ENST00000498400.1 linkuse as main transcript	n.132+135A>G	intron_variant, non_coding_transcript_variant		1
	ENST00000688408.2 linkuse as main transcript	n.367+1069T>C	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98872

AN:

151976

Hom.:

32835

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.625

AC XY:

454442

AN XY:

727058

show subpopulations

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.:

AF XY:

0.650

AC XY:

48336

AN XY:

74378

show subpopulations

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

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.070

T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.0089

LIST_S2

Benign

0.22

T;T

MetaRNN

Benign

8.0e-7

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.50

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

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

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