rs10498801

Variant names:

• chr6-55202166-G-A
• rs10498801
• NM_001384272.1:c.223+27356G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384272.1(HCRTR2):​c.223+27356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,018 control chromosomes in the GnomAD database, including 3,678 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 0.22 (3678 hom., cov: 32)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 6 publications found

Genes affected

HCRTR2 (HGNC:4849): (hypocretin receptor 2) The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein binds the hypothalamic neuropeptides orexin A and orexin B. A related gene (HCRTR1) encodes a G-protein coupled receptor that selectively binds orexin A. [provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384272.1. 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
	HCRTR2	NM_001384272.1	MANE Select	c.223+27356G>A		intron	N/A	NP_001371201.1	S4X0W3
	HCRTR2	NM_001526.5		c.223+27356G>A		intron	N/A	NP_001517.2	O43614

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCRTR2	ENST00000370862.4	TSL:1 MANE Select	c.223+27356G>A		intron	N/A	ENSP00000359899.3	O43614
	HCRTR2	ENST00000615358.4	TSL:1	c.223+27356G>A		intron	N/A	ENSP00000477548.1	O43614

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32706 AN: 151900 Hom.: 3670 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.218

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.215 AC: 32754 AN: 152018 Hom.: 3678 Cov.: 32 AF XY: 0.217 AC XY: 16121 AN XY: 74296

African (AFR) AF: 0.240 AC: 9963 AN: 41470

American (AMR) AF: 0.295 AC: 4513 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1288 AN: 5156

South Asian (SAS) AF: 0.179 AC: 861 AN: 4814

European-Finnish (FIN) AF: 0.199 AC: 2106 AN: 10564

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12735 AN: 67954

Other (OTH) AF: 0.217 AC: 456 AN: 2106

Alfa AF: 0.207 Hom.: 449

Bravo AF: 0.229

Asia WGS AF: 0.218 AC: 758 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.056
DANN	Benign	0.35
PhyloP100		-1.5
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: rs10498801; hg19: chr6-55066964;