Variant chr1-31623620-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001525.3(HCRTR1):c.836G>A(p.Arg279Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00404 in 1,613,850 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 110 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 121 hom. )

Consequence

HCRTR1
NM_001525.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.37

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022182167).

BP6

Variant 1-31623620-G-A is Benign according to our data. Variant chr1-31623620-G-A is described in ClinVar as [Benign]. Clinvar id is 783281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 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.836G>A	p.Arg279Gln	missense_variant	7/9	ENST00000403528.7	NP_001516.2
HCRTR1	XM_024446605.2 linkuse as main transcript	c.836G>A	p.Arg279Gln	missense_variant	8/11		XP_024302373.1
HCRTR1	XM_017001107.2 linkuse as main transcript	c.836G>A	p.Arg279Gln	missense_variant	5/7		XP_016856596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCRTR1	ENST00000403528.7 linkuse as main transcript	c.836G>A	p.Arg279Gln	missense_variant	7/9	5	NM_001525.3	ENSP00000384387	P1

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3346

AN:

152188

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0761

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00955

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00587

AC:

1470

AN:

250576

Hom.:

AF XY:

0.00403

AC XY:

547

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.0805

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00216

AC:

3158

AN:

1461544

Hom.:

121

Cov.:

AF XY:

0.00191

AC XY:

1389

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0753

Gnomad4 AMR exome

AF:

0.00398

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.00518

GnomAD4 genome

AF:

0.0221

AC:

3361

AN:

152306

Hom.:

110

Cov.:

AF XY:

0.0215

AC XY:

1603

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0762

Gnomad4 AMR

AF:

0.00948

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00651

Hom.:

Bravo

AF:

0.0252

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0763

AC:

336

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00736

AC:

894

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.095

T;T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.78

T;.;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.0

M;M;.

MutationTaster

Benign

0.86

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.49

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.063

T;T;T

Sift4G

Benign

0.072

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.14

MVP

0.80

MPC

0.82

ClinPred

0.045

GERP RS

3.9

Varity_R

0.16

gMVP

0.56

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over