6-55202520-A-G

Variant names:

• chr6-55202520-A-G
• rs3134701
• NM_001384272.1:c.223+27710A>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.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
• Publications: 4 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=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384272.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCRTR2	NM_001384272.1	MANE Select	c.223+27710A>G		intron	N/A	NP_001371201.1
	HCRTR2	NM_001526.5		c.223+27710A>G		intron	N/A	NP_001517.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCRTR2	ENST00000370862.4	TSL:1 MANE Select	c.223+27710A>G		intron	N/A	ENSP00000359899.3
	HCRTR2	ENST00000615358.4	TSL:1	c.223+27710A>G		intron	N/A	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

African (AFR) AF: 0.398 AC: 16507 AN: 41494

American (AMR) AF: 0.334 AC: 5105 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1287 AN: 5166

South Asian (SAS) AF: 0.214 AC: 1033 AN: 4826

European-Finnish (FIN) AF: 0.212 AC: 2241 AN: 10578

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14472 AN: 67960

Other (OTH) AF: 0.271 AC: 570 AN: 2104

Alfa AF: 0.250 Hom.: 690

Bravo AF: 0.296

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.40
DANN	Benign	0.30
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3134701; hg19: chr6-55067318;