rs11970116

Variant names:

• chr6-55135347-T-A
• rs11970116
• ENST00000615358.4:c.-378+28802T>A

Variant summary

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

The NM_001526.5(HCRTR2):​c.-378+28802T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,064 control chromosomes in the GnomAD database, including 4,718 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 0.22 (4718 hom., cov: 32)
• Consequence: HCRTR2 NM_001526.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001526.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCRTR2	NM_001526.5		c.-378+28802T>A		intron	N/A	NP_001517.2	O43614

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCRTR2	ENST00000615358.4	TSL:1	c.-378+28802T>A		intron	N/A	ENSP00000477548.1	O43614

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33965 AN: 151946 Hom.: 4721 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0796

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.223 AC: 33959 AN: 152064 Hom.: 4718 Cov.: 32 AF XY: 0.221 AC XY: 16406 AN XY: 74340

African (AFR) AF: 0.0693 AC: 2877 AN: 41534

American (AMR) AF: 0.214 AC: 3267 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3466

East Asian (EAS) AF: 0.0796 AC: 412 AN: 5178

South Asian (SAS) AF: 0.259 AC: 1249 AN: 4828

European-Finnish (FIN) AF: 0.265 AC: 2810 AN: 10594

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21078 AN: 67886

Other (OTH) AF: 0.243 AC: 514 AN: 2112

Alfa AF: 0.269 Hom.: 815

Bravo AF: 0.214

Asia WGS AF: 0.175 AC: 610 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.65
PhyloP100		0.13

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: rs11970116; hg19: chr6-55000145;