rs11970116

chr6-55135347-T-A

Variant summary

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

The ENST00000615358.4(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 ENST00000615358.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCRTR2	NM_001526.5	c.-378+28802T>A		intron_variant
HCRTR2	XM_017010798.2	c.-378+28802T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCRTR2	ENST00000615358.4	c.-378+28802T>A		intron_variant		1		P1

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

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.0796

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.243

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.9
Dann	Benign	0.65

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: rs11970116; hg19: chr6-55000145;