chr1-31622933-T-G

Variant names:

• chr1-31622933-T-G
• rs4949449
• NM_001525.3:c.739-590T>G

Variant summary

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

The NM_001525.3(HCRTR1):​c.739-590T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,068 control chromosomes in the GnomAD database, including 21,166 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 0.51 (21166 hom., cov: 32)
• Consequence: HCRTR1 NM_001525.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 8 publications found

Genes affected

HCRTR1 (HGNC:4848): (hypocretin receptor 1) The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein selectively binds the hypothalamic neuropeptide orexin A. A related gene (HCRTR2) encodes a G-protein coupled receptor that binds orexin A and orexin B. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001525.3. 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
	HCRTR1	NM_001525.3	MANE Select	c.739-590T>G		intron	N/A	NP_001516.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCRTR1	ENST00000403528.7	TSL:5 MANE Select	c.739-590T>G		intron	N/A	ENSP00000384387.2
	HCRTR1	ENST00000373706.9	TSL:1	c.739-590T>G		intron	N/A	ENSP00000362810.5
	HCRTR1	ENST00000373705.1	TSL:1	c.739-590T>G		intron	N/A	ENSP00000362809.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76867 AN: 151950 Hom.: 21159 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.506 AC: 76890 AN: 152068 Hom.: 21166 Cov.: 32 AF XY: 0.505 AC XY: 37551 AN XY: 74336

African (AFR) AF: 0.299 AC: 12406 AN: 41486

American (AMR) AF: 0.515 AC: 7880 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1251 AN: 5160

South Asian (SAS) AF: 0.601 AC: 2897 AN: 4824

European-Finnish (FIN) AF: 0.624 AC: 6592 AN: 10564

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41888 AN: 67960

Other (OTH) AF: 0.523 AC: 1103 AN: 2108

Alfa AF: 0.448 Hom.: 1862

Bravo AF: 0.488

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.75
PhyloP100		-0.0090
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: rs4949449; hg19: chr1-32088534;