ENST00000615358.4:c.-377-17448G>C

Variant names:

• chr6-55156763-G-C
• rs35833281
• ENST00000615358.4:c.-377-17448G>C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.97).
• 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 rank	MANE	Protein	UniProt
HCRTR2	NM_001526.5	c.-377-17448G>C		intron_variant	Intron 1 of 7		NP_001517.2
HCRTR2	XM_017010798.2	c.-377-17448G>C		intron_variant	Intron 1 of 8		XP_016866287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCRTR2	ENST00000615358.4	c.-377-17448G>C		intron_variant	Intron 1 of 7	1		ENSP00000477548.1

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

African (AFR) AF: 0.0416 AC: 1725 AN: 41446

American (AMR) AF: 0.141 AC: 2154 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3466

East Asian (EAS) AF: 0.0277 AC: 143 AN: 5168

South Asian (SAS) AF: 0.113 AC: 544 AN: 4826

European-Finnish (FIN) AF: 0.188 AC: 1977 AN: 10520

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14647 AN: 67930

Other (OTH) AF: 0.169 AC: 356 AN: 2106

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
PhyloP100		-0.34

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: rs35833281; hg19: chr6-55021561;