3-11252624-T-C

Variant summary

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

The NM_001098212.2(HRH1):​c.-35-6379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,996 control chromosomes in the GnomAD database, including 23,990 homozygotes. 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: 𝑓 0.55 ( 23990 hom., cov: 32)
Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

HRH1
NM_001098212.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.968
Variant links:
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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HRH1NM_001098212.2 linkuse as main transcriptc.-35-6379T>C intron_variant ENST00000431010.3
HRH1NM_001098211.2 linkuse as main transcriptc.-35-6379T>C intron_variant
HRH1NM_001098213.2 linkuse as main transcriptc.-35-6379T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HRH1ENST00000431010.3 linkuse as main transcriptc.-35-6379T>C intron_variant 1 NM_001098212.2 P1
HRH1ENST00000413416.1 linkuse as main transcriptc.-35-6379T>C intron_variant 4
HRH1ENST00000438284.2 linkuse as main transcriptc.-35-6379T>C intron_variant 2 P1

Frequencies

GnomAD3 genomes
AF:
0.547
AC:
83030
AN:
151876
Hom.:
23986
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.353
Gnomad AMI
AF:
0.570
Gnomad AMR
AF:
0.486
Gnomad ASJ
AF:
0.553
Gnomad EAS
AF:
0.660
Gnomad SAS
AF:
0.525
Gnomad FIN
AF:
0.643
Gnomad MID
AF:
0.592
Gnomad NFE
AF:
0.655
Gnomad OTH
AF:
0.564
GnomAD4 exome
AF:
0.500
AC:
1
AN:
2
Hom.:
0
AC XY:
0
AN XY:
0
show subpopulations
Gnomad4 OTH exome
AF:
0.500
GnomAD4 genome
AF:
0.546
AC:
83063
AN:
151994
Hom.:
23990
Cov.:
32
AF XY:
0.544
AC XY:
40398
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.352
Gnomad4 AMR
AF:
0.485
Gnomad4 ASJ
AF:
0.553
Gnomad4 EAS
AF:
0.660
Gnomad4 SAS
AF:
0.525
Gnomad4 FIN
AF:
0.643
Gnomad4 NFE
AF:
0.655
Gnomad4 OTH
AF:
0.568
Alfa
AF:
0.580
Hom.:
3934
Bravo
AF:
0.530
Asia WGS
AF:
0.583
AC:
2027
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
6.8
DANN
Benign
0.49

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: rs346074; hg19: chr3-11294310; API