22-40682469-T-C

Position:

• chr22-40682469-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

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]

LOC124905123 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCHR1	NM_005297.4	c.*541T>C		3_prime_UTR_variant	2/2	ENST00000249016.5	NP_005288.4
LOC124905123	XR_007068109.1	n.2462A>G		non_coding_transcript_exon_variant	1/2
LOC124905123	XR_007068110.1	n.189-1692A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCHR1	ENST00000249016.5	c.*541T>C		3_prime_UTR_variant	2/2	1	NM_005297.4	ENSP00000249016.5
ENSG00000289292	ENST00000688408.2	n.198-1692A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68762 AN: 151880 Hom.: 17423 Cov.: 31

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.: 0 AF XY: 0.488 AC XY: 5048 AN XY: 10334

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.922

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.638

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.452 AC: 68765 AN: 151996 Hom.: 17419 Cov.: 31 AF XY: 0.457 AC XY: 33960 AN XY: 74280

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.475

Alfa AF: 0.488 Hom.: 11326

Bravo AF: 0.426

Asia WGS AF: 0.642 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.51

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: rs133074; hg19: chr22-41078473;