rs3800539

Positions:

• chr6-55276221-G-A
• chr6-55276221-G-C

Variant summary

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

The NM_001384272.1(HCRTR2):​c.763-1159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,112 control chromosomes in the GnomAD database, including 3,221 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 0.19 (3221 hom., cov: 33)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCRTR2	NM_001384272.1	c.763-1159G>A		intron_variant		ENST00000370862.4
HCRTR2	NM_001526.5	c.763-1159G>A		intron_variant
HCRTR2	XM_017010798.2	c.763-1159G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCRTR2	ENST00000370862.4	c.763-1159G>A		intron_variant		1	NM_001384272.1	P1
HCRTR2	ENST00000615358.4	c.763-1159G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29001 AN: 151994 Hom.: 3220 Cov.: 33

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.191 AC: 29012 AN: 152112 Hom.: 3221 Cov.: 33 AF XY: 0.191 AC XY: 14208 AN XY: 74334

Gnomad4 AFR AF: 0.0726

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.213

Alfa AF: 0.213 Hom.: 485

Bravo AF: 0.187

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.093
DANN	Benign	0.48

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: rs3800539; hg19: chr6-55141019;