chr22-40679539-A-T

Position:

• chr22-40679539-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005297.4(MCHR1):​c.-114A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MCHR1 NM_005297.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14607787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCHR1	NM_005297.4	c.-114A>T		5_prime_UTR_variant	1/2	ENST00000249016.5	NP_005288.4
LOC124905123	XR_007068110.1	n.358+1069T>A		intron_variant, non_coding_transcript_variant
LOC124905123	XR_007068109.1	n.4323+1069T>A		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.077	T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.075
Sift	Benign	0.034	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.19	B;.
Vest4		0.12
MutPred		0.34		Loss of solvent accessibility (P = 0.0193);Loss of solvent accessibility (P = 0.0193);
MVP		0.65
MPC		0.16
ClinPred		0.22	T
GERP RS		2.0
Varity_R		0.044
gMVP		0.40

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

Other links and lift over

dbSNP: rs133072; hg19: chr22-41075543;