Variant rs2271933 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001525.3(HCRTR1):c.1222A>G(p.Ile408Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,613,344 control chromosomes in the GnomAD database, including 282,591 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.50 ( 20918 hom., cov: 32)

Exomes 𝑓: 0.59 ( 261673 hom. )

Consequence

HCRTR1
NM_001525.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

Variant links:

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]

HCRTR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.4532186E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HCRTR1	NM_001525.3 linkuse as main transcript	c.1222A>G	p.Ile408Val	missense_variant	9/9	ENST00000403528.7	NP_001516.2
HCRTR1	XM_024446605.2 linkuse as main transcript	c.1222A>G	p.Ile408Val	missense_variant	10/11		XP_024302373.1
HCRTR1	XM_017001107.2 linkuse as main transcript	c.1087+1806A>G		intron_variant			XP_016856596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCRTR1	ENST00000403528.7 linkuse as main transcript	c.1222A>G	p.Ile408Val	missense_variant	9/9	5	NM_001525.3	ENSP00000384387	P1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76447

AN:

151896

Hom.:

20912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.653

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.594

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.600

Gnomad FIN

AF:

0.625

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.525

GnomAD3 exomes

AF:

0.556

AC:

139595

AN:

251106

Hom.:

40953

AF XY:

0.570

AC XY:

77399

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.298

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.609

Gnomad EAS exome

AF:

0.251

Gnomad SAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.624

Gnomad NFE exome

AF:

0.617

Gnomad OTH exome

AF:

0.576

GnomAD4 exome

AF:

0.593

AC:

865889

AN:

1461330

Hom.:

261673

Cov.:

AF XY:

0.595

AC XY:

432931

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.604

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.629

Gnomad4 FIN exome

AF:

0.618

Gnomad4 NFE exome

AF:

0.615

Gnomad4 OTH exome

AF:

0.561

GnomAD4 genome

AF:

0.503

AC:

76470

AN:

152014

Hom.:

20918

Cov.:

AF XY:

0.503

AC XY:

37367

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.299

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.594

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.599

Gnomad4 FIN

AF:

0.625

Gnomad4 NFE

AF:

0.612

Gnomad4 OTH

AF:

0.519

Alfa

AF:

0.589

Hom.:

70664

Bravo

AF:

0.486

TwinsUK

AF:

0.622

AC:

2307

ALSPAC

AF:

0.614

AC:

2365

ESP6500AA

AF:

0.310

AC:

1364

ESP6500EA

AF:

0.614

AC:

5281

ExAC

AF:

0.556

AC:

67531

Asia WGS

AF:

0.409

AC:

1424

AN:

3478

EpiCase

AF:

0.614

EpiControl

AF:

0.618

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.036

T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.12

T;.

MetaRNN

Benign

0.000035

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.4

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.45

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.075

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.025

MPC

0.28

ClinPred

0.00057

GERP RS

3.8

Varity_R

0.027

gMVP

0.059

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over