chr22-40679620-C-T

Variant names:

Variant summary

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

The NM_005297.4(MCHR1):c.-33C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,674 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: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

MCHR1
NM_005297.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0210

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:

ENSG00000289292 (HGNC:):

ENSG00000289292 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=0.057383835).

BP6

Variant 22-40679620-C-T is Benign according to our data. Variant chr22-40679620-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3293639.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MCHR1	NM_005297.4 link	c.-33C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000249016.5	NP_005288.4	Q99705
MCHR1	NM_005297.4 link	c.-33C>T	5_prime_UTR_variant	Exon 1 of 2	ENST00000249016.5	NP_005288.4	Q99705
LOC124905123	XR_007068109.1 link	n.4323+988G>A	intron_variant	Intron 1 of 1
LOC124905123	XR_007068110.1 link	n.358+988G>A	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCHR1	ENST00000249016 link	c.-33C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_005297.4	ENSP00000249016.5		Q99705
MCHR1	ENST00000249016 link	c.-33C>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_005297.4	ENSP00000249016.5		Q99705

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249836

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135268

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 09, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.5

DANN

Benign

0.71

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

N;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.086

Sift

Benign

0.13

T;T

Sift4G

Uncertain

0.032

D;D

Polyphen

0.78

P;.

Vest4

0.093

MutPred

0.40

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.49

MPC

0.13

ClinPred

0.075

GERP RS

-1.9

Varity_R

0.037

gMVP

0.53

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