Variant chr22-40679584-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005297.4(MCHR1):c.-69C>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 0.000093 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

MCHR1
NM_005297.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.84

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020835072).

BP6

Variant 22-40679584-C-G is Benign according to our data. Variant chr22-40679584-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3060271.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MCHR1	NM_005297.4 linkuse as main transcript	c.-69C>G	5_prime_UTR_variant	1/2	ENST00000249016.5
LOC124905123	XR_007068110.1 linkuse as main transcript	n.358+1024G>C	intron_variant, non_coding_transcript_variant
LOC124905123	XR_007068109.1 linkuse as main transcript	n.4323+1024G>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
MCHR1	ENST00000249016.5 linkuse as main transcript	c.-69C>G	5_prime_UTR_variant	1/2	1	NM_005297.4	P1
MCHR1	ENST00000381433.3 linkuse as main transcript	c.-69C>G	5_prime_UTR_variant	1/3	1
MCHR1	ENST00000498400.1 linkuse as main transcript	n.132+180C>G	intron_variant, non_coding_transcript_variant		1
	ENST00000688408.2 linkuse as main transcript	n.367+1024G>C	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000149

AC:

AN:

247550

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134364

show subpopulations

Gnomad AFR exome

AF:

0.00200

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461432

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000584

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.000612

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000149

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MCHR1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 13, 2022

This variant is classified as likely 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

0.074

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

T;.

Eigen

Benign

-0.017

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.51

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

N;.

MutationTaster

Benign

0.95

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.016

D;D

Sift4G

Benign

0.24

T;T

Polyphen

0.56

P;.

Vest4

0.22

MVP

0.59

MPC

0.13

ClinPred

0.017

GERP RS

5.0

Varity_R

0.17

gMVP

0.18

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over