chr22-40679528-A-T

Variant names:

• chr22-40679528-A-T
• rs112405400
• NM_005297.4:c.-125A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_005297.4(MCHR1):​c.-125A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,613,458 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0096 (28 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (105 hom.)
• Consequence: MCHR1 NM_005297.4 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.634
• 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]

ENSG00000289292 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039777756).
• BP6: Variant 22-40679528-A-T is Benign according to our data. Variant chr22-40679528-A-T is described in ClinVar as Benign. ClinVar VariationId is 3059605.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00964 (1465/151946) while in subpopulation AFR AF = 0.0175 (725/41416). AF 95% confidence interval is 0.0164. There are 28 homozygotes in GnomAd4. There are 760 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

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.-125A>T		5_prime_UTR	Exon 1 of 2	NP_005288.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCHR1	ENST00000249016.5	TSL:1 MANE Select	c.-125A>T		5_prime_UTR	Exon 1 of 2	ENSP00000249016.5	Q99705
	MCHR1	ENST00000381433.3	TSL:1	c.-125A>T		5_prime_UTR	Exon 1 of 3	ENSP00000370841.3	A6ZJ87
	MCHR1	ENST00000498400.1	TSL:1	n.132+124A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00958 AC: 1455 AN: 151828 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.00346

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00763 AC: 1904 AN: 249648 AF XY: 0.00745

Gnomad AFR exome AF: 0.0157

Gnomad AMR exome AF: 0.00845

Gnomad ASJ exome AF: 0.0670

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00442

Gnomad OTH exome AF: 0.0167

GnomAD4 exome AF: 0.00477 AC: 6973 AN: 1461512 Hom.: 105 Cov.: 31 AF XY: 0.00494 AC XY: 3594 AN XY: 727046

African (AFR) AF: 0.0200 AC: 669 AN: 33478

American (AMR) AF: 0.00921 AC: 412 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 1776 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00305 AC: 263 AN: 86246

European-Finnish (FIN) AF: 0.000207 AC: 11 AN: 53248

Middle Eastern (MID) AF: 0.0514 AC: 296 AN: 5758

European-Non Finnish (NFE) AF: 0.00258 AC: 2867 AN: 1111844

Other (OTH) AF: 0.0112 AC: 679 AN: 60382

GnomAD4 genome AF: 0.00964 AC: 1465 AN: 151946 Hom.: 28 Cov.: 33 AF XY: 0.0102 AC XY: 760 AN XY: 74296

African (AFR) AF: 0.0175 AC: 725 AN: 41416

American (AMR) AF: 0.0143 AC: 218 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 224 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.00344 AC: 234 AN: 67944

Other (OTH) AF: 0.0165 AC: 35 AN: 2116

Alfa AF: 0.00960 Hom.: 24

Bravo AF: 0.0103

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.0148 AC: 65

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00721 AC: 875

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.00747

EpiControl AF: 0.00729

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MCHR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.63
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.070	T
Polyphen		0.42	B
Vest4		0.40
MVP		0.79
MPC		0.19
ClinPred		0.012	T
GERP RS		-0.012
PromoterAI		0.11	Neutral
Varity_R		0.12
gMVP		0.30
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

Other links and lift over

dbSNP: rs112405400; hg19: chr22-41075532;