rs11914085

Variant names:

• chr22-40680966-G-A
• rs11914085
• NM_005297.4:c.100G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005297.4(MCHR1):​c.100G>A​(p.Gly34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00651 in 1,614,002 control chromosomes in the GnomAD database, including 603 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (297 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (306 hom.)
• Consequence: MCHR1 NM_005297.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:4
• Conservation: PhyloP100: 0.0980
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018067956).
• BP6: Variant 22-40680966-G-A is Benign according to our data. Variant chr22-40680966-G-A is described in ClinVar as Benign. ClinVar VariationId is 1284474.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCHR1	NM_005297.4	MANE Select	c.100G>A	p.Gly34Arg	missense	Exon 2 of 2	NP_005288.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCHR1	ENST00000249016.5	TSL:1 MANE Select	c.100G>A	p.Gly34Arg	missense	Exon 2 of 2	ENSP00000249016.5
	MCHR1	ENST00000381433.3	TSL:1	c.100G>A	p.Gly34Arg	missense	Exon 2 of 3	ENSP00000370841.3
	MCHR1	ENST00000465662.1	TSL:1	n.128G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5149 AN: 152040 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.00882 AC: 2217 AN: 251270 AF XY: 0.00638

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00365 AC: 5342 AN: 1461844 Hom.: 306 Cov.: 32 AF XY: 0.00315 AC XY: 2289 AN XY: 727230

African (AFR) AF: 0.130 AC: 4344 AN: 33472

American (AMR) AF: 0.00472 AC: 211 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000249 AC: 277 AN: 1112010

Other (OTH) AF: 0.00767 AC: 463 AN: 60394

GnomAD4 genome AF: 0.0339 AC: 5162 AN: 152158 Hom.: 297 Cov.: 32 AF XY: 0.0326 AC XY: 2423 AN XY: 74376

African (AFR) AF: 0.118 AC: 4898 AN: 41468

American (AMR) AF: 0.0124 AC: 190 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68028

Other (OTH) AF: 0.0223 AC: 47 AN: 2110

Alfa AF: 0.0129 Hom.: 219

Bravo AF: 0.0386

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.121 AC: 534

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0113 AC: 1368

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	MCHR1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.2
DANN	Benign	0.69
DEOGEN2	Benign	0.097	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		0.098
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.017
Sift	Benign	0.59	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.11		Gain of glycosylation at P100 (P = 0.0791)
MPC		0.15
ClinPred		0.0028	T
GERP RS		1.6
Varity_R		0.044
gMVP		0.69
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs11914085; hg19: chr22-41076970;