6-55156763-G-C

Position:

• chr6-55156763-G-C

Variant summary

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

The ENST00000615358.4(HCRTR2):​c.-377-17448G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,914 control chromosomes in the GnomAD database, including 2,162 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 0.15 (2162 hom., cov: 32)
• Consequence: HCRTR2 ENST00000615358.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCRTR2	NM_001526.5	c.-377-17448G>C		intron_variant			NP_001517.2
HCRTR2	XM_017010798.2	c.-377-17448G>C		intron_variant			XP_016866287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCRTR2	ENST00000615358.4	c.-377-17448G>C		intron_variant		1		ENSP00000477548	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22277 AN: 151796 Hom.: 2165 Cov.: 32

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0278

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.147 AC: 22276 AN: 151914 Hom.: 2162 Cov.: 32 AF XY: 0.144 AC XY: 10671 AN XY: 74222

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0277

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.169

Alfa AF: 0.166 Hom.: 326

Bravo AF: 0.139

Asia WGS AF: 0.0850 AC: 293 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.74
DANN	Benign	0.64

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: rs35833281; hg19: chr6-55021561;