NM_001384272.1:c.223+28019C>A

Variant names:

• chr6-55202829-C-A
• rs6937878
• NM_001384272.1:c.223+28019C>A

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+28019C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,888 control chromosomes in the GnomAD database, including 5,081 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 0.25 (5081 hom., cov: 31)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCRTR2	NM_001384272.1	c.223+28019C>A		intron_variant	Intron 1 of 6	ENST00000370862.4	NP_001371201.1
HCRTR2	NM_001526.5	c.223+28019C>A		intron_variant	Intron 2 of 7		NP_001517.2
HCRTR2	XM_017010798.2	c.223+28019C>A		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.223+28019C>A		intron_variant	Intron 1 of 6	1	NM_001384272.1	ENSP00000359899.3
HCRTR2	ENST00000615358.4	c.223+28019C>A		intron_variant	Intron 2 of 7	1		ENSP00000477548.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37438 AN: 151768 Hom.: 5064 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.247 AC: 37501 AN: 151888 Hom.: 5081 Cov.: 31 AF XY: 0.248 AC XY: 18381 AN XY: 74238

African (AFR) AF: 0.350 AC: 14469 AN: 41392

American (AMR) AF: 0.308 AC: 4689 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3464

East Asian (EAS) AF: 0.248 AC: 1273 AN: 5132

South Asian (SAS) AF: 0.180 AC: 865 AN: 4808

European-Finnish (FIN) AF: 0.199 AC: 2104 AN: 10568

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12756 AN: 67966

Other (OTH) AF: 0.240 AC: 506 AN: 2108

Alfa AF: 0.209 Hom.: 13507

Bravo AF: 0.265

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.087
DANN	Benign	0.40
PhyloP100		-1.2
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: rs6937878; hg19: chr6-55067627;