Genetic Variant MCHR1:c.*541T>C (chr22-40682469-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005297.4(MCHR1):c.*541T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 171,558 control chromosomes in the GnomAD database, including 20,172 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 0.45 ( 17419 hom., cov: 31)

Exomes 𝑓: 0.49 ( 2753 hom. )

Consequence

MCHR1
NM_005297.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.275

Publications

17 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005297.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCHR1	NM_005297.4	MANE Select	c.*541T>C		3_prime_UTR	Exon 2 of 2	NP_005288.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MCHR1	ENST00000249016.5	TSL:1 MANE Select	c.*541T>C	3_prime_UTR	Exon 2 of 2	ENSP00000249016.5	Q99705
ENSG00000289292	ENST00000764110.1		n.1209A>G	non_coding_transcript_exon	Exon 2 of 2
ENSG00000289292	ENST00000688408.3		n.206-1692A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68762

AN:

151880

Hom.:

17423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.902

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.643

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.487

AC:

9531

AN:

19562

Hom.:

2753

Cov.:

AF XY:

0.488

AC XY:

5048

AN XY:

10334

show subpopulations

African (AFR)

AF:

0.221

AC:

146

AN:

660

American (AMR)

AF:

0.313

AC:

1027

AN:

3282

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

AN:

222

East Asian (EAS)

AF:

0.922

AC:

1756

AN:

1904

South Asian (SAS)

AF:

0.426

AC:

979

AN:

2296

European-Finnish (FIN)

AF:

0.638

AC:

462

AN:

724

Middle Eastern (MID)

AF:

0.357

AC:

AN:

European-Non Finnish (NFE)

AF:

0.486

AC:

4702

AN:

9674

Other (OTH)

AF:

0.472

AC:

358

AN:

758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

192

385

577

770

962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.452

AC:

68765

AN:

151996

Hom.:

17419

Cov.:

AF XY:

0.457

AC XY:

33960

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.262

AC:

10881

AN:

41490

American (AMR)

AF:

0.351

AC:

5354

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1710

AN:

3468

East Asian (EAS)

AF:

0.902

AC:

4661

AN:

5168

South Asian (SAS)

AF:

0.446

AC:

2146

AN:

4816

European-Finnish (FIN)

AF:

0.643

AC:

6791

AN:

10554

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.524

AC:

35634

AN:

67942

Other (OTH)

AF:

0.475

AC:

1002

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1734

3467

5201

6934

8668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.496

Hom.:

45111

Bravo

AF:

0.426

Asia WGS

AF:

0.642

AC:

2230

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.6

(source)

DANN

Benign

0.51

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over