chr22-40679528-A-T
Position:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_005297.4(MCHR1):c.-125A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,613,458 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0096 ( 28 hom., cov: 33)
Exomes 𝑓: 0.0048 ( 105 hom. )
Consequence
MCHR1
NM_005297.4 5_prime_UTR
NM_005297.4 5_prime_UTR
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 0.634
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0039777756).
BP6
Variant 22-40679528-A-T is Benign according to our data. Variant chr22-40679528-A-T is described in ClinVar as [Benign]. Clinvar id is 3059605.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-40679528-A-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00964 (1465/151946) while in subpopulation AFR AF= 0.0175 (725/41416). AF 95% confidence interval is 0.0164. There are 28 homozygotes in gnomad4. There are 760 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 28 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCHR1 | NM_005297.4 | c.-125A>T | 5_prime_UTR_variant | 1/2 | ENST00000249016.5 | ||
LOC124905123 | XR_007068110.1 | n.358+1080T>A | intron_variant, non_coding_transcript_variant | ||||
LOC124905123 | XR_007068109.1 | n.4323+1080T>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCHR1 | ENST00000249016.5 | c.-125A>T | 5_prime_UTR_variant | 1/2 | 1 | NM_005297.4 | P1 | ||
MCHR1 | ENST00000381433.3 | c.-125A>T | 5_prime_UTR_variant | 1/3 | 1 | ||||
MCHR1 | ENST00000498400.1 | n.132+124A>T | intron_variant, non_coding_transcript_variant | 1 | |||||
ENST00000688408.2 | n.367+1080T>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00958 AC: 1455AN: 151828Hom.: 27 Cov.: 33
GnomAD3 genomes
AF:
AC:
1455
AN:
151828
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00763 AC: 1904AN: 249648Hom.: 41 AF XY: 0.00745 AC XY: 1007AN XY: 135198
GnomAD3 exomes
AF:
AC:
1904
AN:
249648
Hom.:
AF XY:
AC XY:
1007
AN XY:
135198
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00477 AC: 6973AN: 1461512Hom.: 105 Cov.: 31 AF XY: 0.00494 AC XY: 3594AN XY: 727046
GnomAD4 exome
AF:
AC:
6973
AN:
1461512
Hom.:
Cov.:
31
AF XY:
AC XY:
3594
AN XY:
727046
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00964 AC: 1465AN: 151946Hom.: 28 Cov.: 33 AF XY: 0.0102 AC XY: 760AN XY: 74296
GnomAD4 genome
AF:
AC:
1465
AN:
151946
Hom.:
Cov.:
33
AF XY:
AC XY:
760
AN XY:
74296
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
10
ALSPAC
AF:
AC:
10
ESP6500AA
AF:
AC:
65
ESP6500EA
AF:
AC:
57
ExAC
AF:
AC:
875
Asia WGS
AF:
AC:
26
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MCHR1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 02, 2019 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;D
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at