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GeneBe

1-31619569-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001525.3(HCRTR1):c.237A>G(p.Thr79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,614,126 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0043 ( 12 hom. )

Consequence

HCRTR1
NM_001525.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.57
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-31619569-A-G is Benign according to our data. Variant chr1-31619569-A-G is described in ClinVar as [Benign]. Clinvar id is 779395.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.57 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HCRTR1NM_001525.3 linkuse as main transcriptc.237A>G p.Thr79= synonymous_variant 4/9 ENST00000403528.7
HCRTR1XM_024446605.2 linkuse as main transcriptc.237A>G p.Thr79= synonymous_variant 5/11
HCRTR1XM_017001107.2 linkuse as main transcriptc.237A>G p.Thr79= synonymous_variant 2/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HCRTR1ENST00000403528.7 linkuse as main transcriptc.237A>G p.Thr79= synonymous_variant 4/95 NM_001525.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00308
AC:
469
AN:
152194
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.000864
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00527
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00523
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00362
AC:
908
AN:
251136
Hom.:
2
AF XY:
0.00361
AC XY:
490
AN XY:
135786
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.000434
Gnomad ASJ exome
AF:
0.000497
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00111
Gnomad FIN exome
AF:
0.00653
Gnomad NFE exome
AF:
0.00608
Gnomad OTH exome
AF:
0.00261
GnomAD4 exome
AF:
0.00431
AC:
6302
AN:
1461814
Hom.:
12
Cov.:
33
AF XY:
0.00421
AC XY:
3065
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.000657
Gnomad4 AMR exome
AF:
0.000582
Gnomad4 ASJ exome
AF:
0.000421
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000893
Gnomad4 FIN exome
AF:
0.00639
Gnomad4 NFE exome
AF:
0.00507
Gnomad4 OTH exome
AF:
0.00301
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00308
AC:
469
AN:
152312
Hom.:
2
Cov.:
33
AF XY:
0.00294
AC XY:
219
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000722
Gnomad4 AMR
AF:
0.000653
Gnomad4 ASJ
AF:
0.000864
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00527
Gnomad4 NFE
AF:
0.00523
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00422
Hom.:
1
Bravo
AF:
0.00264
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00414
EpiControl
AF:
0.00433

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
Cadd
Benign
0.012
Dann
Benign
0.52

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.

Other links and lift over

dbSNP: rs111252644; hg19: chr1-32085170; API