chr22-40679691-C-T

Variant names:

• chr22-40679691-C-T
• rs133073
• NM_005297.4:c.39C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005297.4(MCHR1):​c.39C>T​(p.Asn13Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,613,616 control chromosomes in the GnomAD database, including 300,479 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 0.60 (28010 hom., cov: 31)
  • Exomes 𝑓: 0.60 (272469 hom.)
• Consequence: MCHR1 NM_005297.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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]

ENSG00000289292 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCHR1	NM_005297.4	c.39C>T	p.Asn13Asn	synonymous_variant	Exon 1 of 2	ENST00000249016.5	NP_005288.4
LOC124905123	XR_007068109.1	n.4323+917G>A		intron_variant	Intron 1 of 1
LOC124905123	XR_007068110.1	n.358+917G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCHR1	ENST00000249016.5	c.39C>T	p.Asn13Asn	synonymous_variant	Exon 1 of 2	1	NM_005297.4	ENSP00000249016.5
MCHR1	ENST00000381433.3	c.39C>T	p.Asn13Asn	synonymous_variant	Exon 1 of 3	1		ENSP00000370841.3
MCHR1	ENST00000498400.1	n.132+287C>T		intron_variant	Intron 1 of 1	1
ENSG00000289292	ENST00000688408.2	n.367+917G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91089 AN: 151800 Hom.: 27989 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.591

GnomAD2 exomes AF: 0.588 AC: 146332 AN: 249066 AF XY: 0.589

Gnomad AFR exome AF: 0.577

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.556

Gnomad EAS exome AF: 0.982

Gnomad FIN exome AF: 0.672

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.603 AC: 881558 AN: 1461698 Hom.: 272469 Cov.: 65 AF XY: 0.601 AC XY: 436890 AN XY: 727168

Gnomad4 AFR exome AF: 0.572 AC: 19133 AN: 33470

Gnomad4 AMR exome AF: 0.364 AC: 16258 AN: 44722

Gnomad4 ASJ exome AF: 0.550 AC: 14385 AN: 26136

Gnomad4 EAS exome AF: 0.990 AC: 39289 AN: 39696

Gnomad4 SAS exome AF: 0.455 AC: 39257 AN: 86256

Gnomad4 FIN exome AF: 0.671 AC: 35851 AN: 53404

Gnomad4 NFE exome AF: 0.610 AC: 678107 AN: 1111856

Gnomad4 Remaining exome AF: 0.599 AC: 36154 AN: 60390

GnomAD4 genome AF: 0.600 AC: 91148 AN: 151918 Hom.: 28010 Cov.: 31 AF XY: 0.600 AC XY: 44535 AN XY: 74226

Gnomad4 AFR AF: 0.578 AC: 0.577746 AN: 0.577746

Gnomad4 AMR AF: 0.469 AC: 0.46877 AN: 0.46877

Gnomad4 ASJ AF: 0.565 AC: 0.564591 AN: 0.564591

Gnomad4 EAS AF: 0.977 AC: 0.977317 AN: 0.977317

Gnomad4 SAS AF: 0.469 AC: 0.468581 AN: 0.468581

Gnomad4 FIN AF: 0.664 AC: 0.664326 AN: 0.664326

Gnomad4 NFE AF: 0.616 AC: 0.616165 AN: 0.616165

Gnomad4 OTH AF: 0.597 AC: 0.596682 AN: 0.596682

Alfa AF: 0.610 Hom.: 59634

Bravo AF: 0.587

Asia WGS AF: 0.691 AC: 2399 AN: 3478

EpiCase AF: 0.607

EpiControl AF: 0.622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.6
DANN	Benign	0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs133073; hg19: chr22-41075695; COSMIC: COSV50760998; COSMIC: COSV50760998;