18-24477491-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_021624.4(HRH4):c.1102G>A(p.Ala368Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000686 in 1,457,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
HRH4
NM_021624.4 missense
NM_021624.4 missense
Scores
4
4
11
Clinical Significance
Conservation
PhyloP100: 6.85
Genes affected
HRH4 (HGNC:17383): (histamine receptor H4) Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by a family of histamine receptors, which are a subset of the G-protein coupled receptor superfamily. This gene encodes a histamine receptor that is predominantly expressed in haematopoietic cells. The protein is thought to play a role in inflammation and allergy reponses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
Genome browser will be placed here
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=0.38302535).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRH4 | NM_021624.4 | c.1102G>A | p.Ala368Thr | missense_variant | 3/3 | ENST00000256906.5 | |
HRH4 | NM_001143828.2 | c.838G>A | p.Ala280Thr | missense_variant | 2/2 | ||
HRH4 | NM_001160166.2 | c.*734G>A | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRH4 | ENST00000256906.5 | c.1102G>A | p.Ala368Thr | missense_variant | 3/3 | 1 | NM_021624.4 | P1 | |
HRH4 | ENST00000426880.2 | c.838G>A | p.Ala280Thr | missense_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248260Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134410
GnomAD3 exomes
AF:
AC:
4
AN:
248260
Hom.:
AF XY:
AC XY:
4
AN XY:
134410
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000686 AC: 10AN: 1457926Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 725134
GnomAD4 exome
AF:
AC:
10
AN:
1457926
Hom.:
Cov.:
32
AF XY:
AC XY:
8
AN XY:
725134
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
AF:
AC:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | The c.1102G>A (p.A368T) alteration is located in exon 3 (coding exon 3) of the HRH4 gene. This alteration results from a G to A substitution at nucleotide position 1102, causing the alanine (A) at amino acid position 368 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of ubiquitination at K363 (P = 0.0603);.;
MVP
MPC
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