rs2067470
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001098212.2(HRH1):c.1346T>C(p.Leu449Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
HRH1
NM_001098212.2 missense
NM_001098212.2 missense
Scores
5
13
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.06
Genes affected
HRH1 (HGNC:5182): (histamine receptor H1) Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. The protein encoded by this gene is an integral membrane protein and belongs to the G protein-coupled receptor superfamily. It mediates the contraction of smooth muscles, the increase in capillary permeability due to contraction of terminal venules, the release of catecholamine from adrenal medulla, and neurotransmission in the central nervous system. It has been associated with multiple processes, including memory and learning, circadian rhythm, and thermoregulation. It is also known to contribute to the pathophysiology of allergic diseases such as atopic dermatitis, asthma, anaphylaxis and allergic rhinitis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3375491).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRH1 | NM_001098212.2 | c.1346T>C | p.Leu449Ser | missense_variant | 2/2 | ENST00000431010.3 | |
HRH1 | NM_000861.3 | c.1346T>C | p.Leu449Ser | missense_variant | 3/3 | ||
HRH1 | NM_001098211.2 | c.1346T>C | p.Leu449Ser | missense_variant | 2/2 | ||
HRH1 | NM_001098213.2 | c.1346T>C | p.Leu449Ser | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRH1 | ENST00000431010.3 | c.1346T>C | p.Leu449Ser | missense_variant | 2/2 | 1 | NM_001098212.2 | P1 | |
HRH1 | ENST00000397056.1 | c.1346T>C | p.Leu449Ser | missense_variant | 3/3 | 1 | P1 | ||
HRH1 | ENST00000438284.2 | c.1346T>C | p.Leu449Ser | missense_variant | 2/2 | 2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461888Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727244
GnomAD4 exome
AF:
AC:
2
AN:
1461888
Hom.:
Cov.:
34
AF XY:
AC XY:
2
AN XY:
727244
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
B;B;B
Vest4
MutPred
Gain of glycosylation at L449 (P = 0.02);Gain of glycosylation at L449 (P = 0.02);Gain of glycosylation at L449 (P = 0.02);
MVP
MPC
0.77
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at