rs9611386

Positions:

• chr22-40682529-A-G

Variant summary

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

The NM_005297.4(MCHR1):​c.*601A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 158,318 control chromosomes in the GnomAD database, including 1,091 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 0.099 (1080 hom., cov: 31)
  • Exomes 𝑓: 0.045 (11 hom.)
• Consequence: MCHR1 NM_005297.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCHR1	NM_005297.4	c.*601A>G		3_prime_UTR_variant	2/2	ENST00000249016.5	NP_005288.4
LOC124905123	XR_007068109.1	n.2402T>C		non_coding_transcript_exon_variant	1/2
LOC124905123	XR_007068110.1	n.189-1752T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCHR1	ENST00000249016.5	c.*601A>G		3_prime_UTR_variant	2/2	1	NM_005297.4	ENSP00000249016.5
ENSG00000289292	ENST00000688408.2	n.198-1752T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14971 AN: 151998 Hom.: 1077 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0742

GnomAD4 exome AF: 0.0445 AC: 276 AN: 6202 Hom.: 11 Cov.: 0 AF XY: 0.0471 AC XY: 155 AN XY: 3290

Gnomad4 AFR exome AF: 0.0385

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0705

Gnomad4 SAS exome AF: 0.0380

Gnomad4 FIN exome AF: 0.0216

Gnomad4 NFE exome AF: 0.0499

Gnomad4 OTH exome AF: 0.0455

GnomAD4 genome AF: 0.0985 AC: 14988 AN: 152116 Hom.: 1080 Cov.: 31 AF XY: 0.0966 AC XY: 7187 AN XY: 74380

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0778

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.0873

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0575

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0664 Hom.: 308

Bravo AF: 0.104

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.4
DANN	Benign	0.86

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: rs9611386; hg19: chr22-41078533;