chr6-55283305-G-A

Variant names:

• chr6-55283305-G-A
• rs9367630
• XM_017010798.2:c.1331+855G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017010798.2(HCRTR2):​c.1331+855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 152,238 control chromosomes in the GnomAD database, including 663 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 0.037 (663 hom., cov: 32)
• Consequence: HCRTR2 XM_017010798.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766
• Publications: 8 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5565 AN: 152120 Hom.: 655 Cov.: 32

Gnomad AFR AF: 0.00825

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.0279

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00370

Gnomad OTH AF: 0.0416

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

GnomAD4 genome AF: 0.0367 AC: 5585 AN: 152238 Hom.: 663 Cov.: 32 AF XY: 0.0412 AC XY: 3064 AN XY: 74412

African (AFR) AF: 0.00825 AC: 343 AN: 41554

American (AMR) AF: 0.199 AC: 3033 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1550 AN: 5158

South Asian (SAS) AF: 0.0275 AC: 133 AN: 4830

European-Finnish (FIN) AF: 0.0155 AC: 164 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00370 AC: 252 AN: 68032

Other (OTH) AF: 0.0431 AC: 91 AN: 2112

Alfa AF: 0.0222 Hom.: 825

Bravo AF: 0.0514

Asia WGS AF: 0.153 AC: 532 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.4
DANN	Benign	0.77
PhyloP100		0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9367630; hg19: chr6-55148103;