NM_001098212.2:c.-35-10567G>T

Variant names:

• chr3-11248436-G-T
• rs347591
• NM_001098212.2:c.-35-10567G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098212.2(HRH1):​c.-35-10567G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,002 control chromosomes in the GnomAD database, including 26,311 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 0.58 (26311 hom., cov: 31)
• Consequence: HRH1 NM_001098212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954
• Publications: 15 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098212.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH1	NM_001098212.2	MANE Select	c.-35-10567G>T		intron	N/A	NP_001091682.1
	HRH1	NM_001098211.2		c.-35-10567G>T		intron	N/A	NP_001091681.1
	HRH1	NM_001098213.2		c.-35-10567G>T		intron	N/A	NP_001091683.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH1	ENST00000431010.3	TSL:1 MANE Select	c.-35-10567G>T		intron	N/A	ENSP00000397028.2
	HRH1	ENST00000438284.2	TSL:2	c.-35-10567G>T		intron	N/A	ENSP00000406705.2
	HRH1	ENST00000413416.1	TSL:4	c.-35-10567G>T		intron	N/A	ENSP00000392383.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88380 AN: 151884 Hom.: 26306 Cov.: 31

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.582 AC: 88428 AN: 152002 Hom.: 26311 Cov.: 31 AF XY: 0.579 AC XY: 43028 AN XY: 74272

African (AFR) AF: 0.467 AC: 19339 AN: 41442

American (AMR) AF: 0.500 AC: 7635 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1913 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3644 AN: 5152

South Asian (SAS) AF: 0.535 AC: 2577 AN: 4820

European-Finnish (FIN) AF: 0.645 AC: 6804 AN: 10556

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44581 AN: 67964

Other (OTH) AF: 0.588 AC: 1242 AN: 2114

Alfa AF: 0.636 Hom.: 33478

Bravo AF: 0.570

Asia WGS AF: 0.612 AC: 2129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.33
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs347591; hg19: chr3-11290122;