rs3122156

Variant names:

• chr6-55218009-T-G
• rs3122156
• NM_001384272.1:c.224-30630T>G

Variant summary

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

The NM_001384272.1(HCRTR2):​c.224-30630T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,040 control chromosomes in the GnomAD database, including 10,855 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 0.36 (10855 hom., cov: 32)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCRTR2	NM_001384272.1	c.224-30630T>G		intron_variant	Intron 1 of 6	ENST00000370862.4	NP_001371201.1
HCRTR2	NM_001526.5	c.224-30630T>G		intron_variant	Intron 2 of 7		NP_001517.2
HCRTR2	XM_017010798.2	c.224-30630T>G		intron_variant	Intron 2 of 8		XP_016866287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCRTR2	ENST00000370862.4	c.224-30630T>G		intron_variant	Intron 1 of 6	1	NM_001384272.1	ENSP00000359899.3
HCRTR2	ENST00000615358.4	c.224-30630T>G		intron_variant	Intron 2 of 7	1		ENSP00000477548.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53895 AN: 151922 Hom.: 10820 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.355 AC: 53997 AN: 152040 Hom.: 10855 Cov.: 32 AF XY: 0.355 AC XY: 26395 AN XY: 74316

African (AFR) AF: 0.554 AC: 22989 AN: 41470

American (AMR) AF: 0.369 AC: 5634 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3464

East Asian (EAS) AF: 0.234 AC: 1208 AN: 5154

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4824

European-Finnish (FIN) AF: 0.305 AC: 3219 AN: 10564

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17980 AN: 67972

Other (OTH) AF: 0.352 AC: 744 AN: 2112

Alfa AF: 0.298 Hom.: 24363

Bravo AF: 0.373

Asia WGS AF: 0.263 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.80
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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: rs3122156; hg19: chr6-55082807;