rs6937878

chr6-55202829-C-A

Variant summary

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

The NM_001384272.1(HCRTR2):c.223+28019C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,888 control chromosomes in the GnomAD database, including 5,081 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 0.25 (5081 hom., cov: 31)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCRTR2	NM_001384272.1	c.223+28019C>A		intron_variant		ENST00000370862.4
HCRTR2	NM_001526.5	c.223+28019C>A		intron_variant
HCRTR2	XM_017010798.2	c.223+28019C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCRTR2	ENST00000370862.4	c.223+28019C>A		intron_variant		1	NM_001384272.1	P1
HCRTR2	ENST00000615358.4	c.223+28019C>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37438 AN: 151768 Hom.: 5064 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.247 AC: 37501 AN: 151888 Hom.: 5081 Cov.: 31 AF XY: 0.248 AC XY: 18381 AN XY: 74238

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.240

Alfa AF: 0.200 Hom.: 5187

Bravo AF: 0.265

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.087
Dann	Benign	0.40

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: rs6937878; hg19: chr6-55067627;