chr1-31622570-T-C

Position:

• chr1-31622570-T-C

Variant summary

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

The NM_001525.3(HCRTR1):​c.739-953T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,730 control chromosomes in the GnomAD database, including 21,168 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 (21168 hom., cov: 30)
• Consequence: HCRTR1 NM_001525.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCRTR1	NM_001525.3	c.739-953T>C		intron_variant		ENST00000403528.7
HCRTR1	XM_017001107.2	c.739-953T>C		intron_variant
HCRTR1	XM_024446605.2	c.739-953T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCRTR1	ENST00000403528.7	c.739-953T>C		intron_variant		5	NM_001525.3	P1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76863 AN: 151614 Hom.: 21161 Cov.: 30

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.507 AC: 76887 AN: 151730 Hom.: 21168 Cov.: 30 AF XY: 0.506 AC XY: 37522 AN XY: 74108

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.524

Alfa AF: 0.556 Hom.: 3042

Bravo AF: 0.489

Asia WGS AF: 0.413 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs10914456; hg19: chr1-32088171; COSMIC: COSV65484968;