rs9357855

Variant names:

• chr6-55252502-G-A
• rs9357855
• NM_001384272.1:c.403-2634G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-55252502-G-A
• chr6-55252502-G-C
• chr6-55252502-G-T

Variant summary

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

The NM_001384272.1(HCRTR2):​c.403-2634G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,032 control chromosomes in the GnomAD database, including 2,788 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 0.17 (2788 hom., cov: 32)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCRTR2	NM_001384272.1	c.403-2634G>A		intron_variant	Intron 2 of 6	ENST00000370862.4	NP_001371201.1
HCRTR2	NM_001526.5	c.403-2634G>A		intron_variant	Intron 3 of 7		NP_001517.2
HCRTR2	XM_017010798.2	c.403-2634G>A		intron_variant	Intron 3 of 8		XP_016866287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCRTR2	ENST00000370862.4	c.403-2634G>A		intron_variant	Intron 2 of 6	1	NM_001384272.1	ENSP00000359899.3
HCRTR2	ENST00000615358.4	c.403-2634G>A		intron_variant	Intron 3 of 7	1		ENSP00000477548.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26340 AN: 151914 Hom.: 2789 Cov.: 32

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.173 AC: 26338 AN: 152032 Hom.: 2788 Cov.: 32 AF XY: 0.173 AC XY: 12836 AN XY: 74312

Gnomad4 AFR AF: 0.0534

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.196

Alfa AF: 0.120 Hom.: 219

Bravo AF: 0.165

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.5
DANN	Benign	0.60

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: rs9357855; hg19: chr6-55117300;