3-11191093-G-C

Variant names:

• chr3-11191093-G-C
• rs4684059
• NM_001098212.2:c.-36+36539G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HRH1	NM_001098212.2	c.-36+36539G>C		intron_variant	Intron 1 of 1	ENST00000431010.3	NP_001091682.1
HRH1	NM_001098213.2	c.-36+53694G>C		intron_variant	Intron 1 of 1		NP_001091683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HRH1	ENST00000431010.3	c.-36+36539G>C		intron_variant	Intron 1 of 1	1	NM_001098212.2	ENSP00000397028.2
HRH1	ENST00000438284.2	c.-36+53694G>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.257 AC: 10659 AN: 41434

American (AMR) AF: 0.333 AC: 5087 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1086 AN: 3458

East Asian (EAS) AF: 0.429 AC: 2213 AN: 5158

South Asian (SAS) AF: 0.359 AC: 1733 AN: 4822

European-Finnish (FIN) AF: 0.470 AC: 4958 AN: 10556

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27760 AN: 67964

Other (OTH) AF: 0.367 AC: 773 AN: 2106

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
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4684059; hg19: chr3-11232779;