rs3134701

Positions:

• chr6-55202520-A-G
• chr6-55202520-A-T

Variant summary

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

The NM_001384272.1(HCRTR2):​c.223+27710A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,074 control chromosomes in the GnomAD database, including 6,438 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 0.28 (6438 hom., cov: 32)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCRTR2	NM_001384272.1	c.223+27710A>G		intron_variant		ENST00000370862.4	NP_001371201.1
HCRTR2	NM_001526.5	c.223+27710A>G		intron_variant			NP_001517.2
HCRTR2	XM_017010798.2	c.223+27710A>G		intron_variant			XP_016866287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCRTR2	ENST00000370862.4	c.223+27710A>G		intron_variant		1	NM_001384272.1	ENSP00000359899.3
HCRTR2	ENST00000615358.4	c.223+27710A>G		intron_variant		1		ENSP00000477548.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42091 AN: 151956 Hom.: 6412 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.277 AC: 42165 AN: 152074 Hom.: 6438 Cov.: 32 AF XY: 0.277 AC XY: 20592 AN XY: 74324

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.271

Alfa AF: 0.244 Hom.: 625

Bravo AF: 0.296

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.40
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3134701; hg19: chr6-55067318;