3-11191093-G-C

Position:

• chr3-11191093-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098212.2(HRH1):​c.-36+36539G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,956 control chromosomes in the GnomAD database, including 10,390 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 0.36 (10390 hom., cov: 31)
• Consequence: HRH1 NM_001098212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH1	NM_001098212.2	c.-36+36539G>C		intron_variant		ENST00000431010.3	NP_001091682.1
HRH1	NM_001098213.2	c.-36+53694G>C		intron_variant			NP_001091683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRH1	ENST00000431010.3	c.-36+36539G>C		intron_variant		1	NM_001098212.2	ENSP00000397028.2
HRH1	ENST00000438284.2	c.-36+53694G>C		intron_variant		2		ENSP00000406705.2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54862 AN: 151838 Hom.: 10372 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.361 AC: 54908 AN: 151956 Hom.: 10390 Cov.: 31 AF XY: 0.366 AC XY: 27151 AN XY: 74272

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.367

Alfa AF: 0.380 Hom.: 1574

Bravo AF: 0.348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs4684059; hg19: chr3-11232779;