17-42185329-A-G

Variant names:

• chr17-42185329-A-G
• rs9902709
• NM_001524.1:c.21+16T>C

Variant summary

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

The NM_001524.1(HCRT):​c.21+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,613,018 control chromosomes in the GnomAD database, including 7,654 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 0.13 (4031 hom., cov: 32)
  • Exomes 𝑓: 0.014 (3623 hom.)
• Consequence: HCRT NM_001524.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

Genes affected

HCRT (HGNC:4847): (hypocretin neuropeptide precursor) This gene encodes a hypothalamic neuropeptide precursor protein that gives rise to two mature neuropeptides, orexin A and orexin B, by proteolytic processing. Orexin A and orexin B, which bind to orphan G-protein coupled receptors HCRTR1 and HCRTR2, function in the regulation of sleep and arousal. This neuropeptide arrangement may also play a role in feeding behavior, metabolism, and homeostasis. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCRT	NM_001524.1	c.21+16T>C		intron_variant	Intron 1 of 1	ENST00000293330.1	NP_001515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCRT	ENST00000293330.1	c.21+16T>C		intron_variant	Intron 1 of 1	1	NM_001524.1	ENSP00000293330.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19038 AN: 151882 Hom.: 4000 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0445

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0209

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.0876

GnomAD3 exomes AF: 0.0344 AC: 8643 AN: 251340 Hom.: 1640 AF XY: 0.0259 AC XY: 3519 AN XY: 135862

Gnomad AFR exome AF: 0.446

Gnomad AMR exome AF: 0.0201

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.0181

Gnomad SAS exome AF: 0.00444

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.0166

GnomAD4 exome AF: 0.0140 AC: 20523 AN: 1461018 Hom.: 3623 Cov.: 30 AF XY: 0.0124 AC XY: 9041 AN XY: 726868

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.0229

Gnomad4 ASJ exome AF: 0.000804

Gnomad4 EAS exome AF: 0.0345

Gnomad4 SAS exome AF: 0.00479

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000603

Gnomad4 OTH exome AF: 0.0307

GnomAD4 genome AF: 0.126 AC: 19119 AN: 152000 Hom.: 4031 Cov.: 32 AF XY: 0.122 AC XY: 9077 AN XY: 74298

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.0444

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0209

Gnomad4 SAS AF: 0.00664

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00129

Gnomad4 OTH AF: 0.0867

Alfa AF: 0.0218 Hom.: 968

Bravo AF: 0.143

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.36

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: rs9902709; hg19: chr17-40337347;