3-11262188-T-C

Variant names:

• chr3-11262188-T-C
• rs346070
• NM_001098212.2:c.*1687T>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.*1687T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 167,124 control chromosomes in the GnomAD database, including 61,706 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 0.85 (55824 hom., cov: 33)
  • Exomes 𝑓: 0.89 (5882 hom.)
• Consequence: HRH1 NM_001098212.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749
• Publications: 17 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.*1687T>C		3_prime_UTR	Exon 2 of 2	NP_001091682.1
	HRH1	NM_000861.3		c.*1687T>C		3_prime_UTR	Exon 3 of 3	NP_000852.1
	HRH1	NM_001098211.2		c.*1687T>C		3_prime_UTR	Exon 2 of 2	NP_001091681.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH1	ENST00000431010.3	TSL:1 MANE Select	c.*1687T>C		3_prime_UTR	Exon 2 of 2	ENSP00000397028.2
	HRH1	ENST00000397056.1	TSL:1	c.*1687T>C		3_prime_UTR	Exon 3 of 3	ENSP00000380247.1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 130051 AN: 152122 Hom.: 55776 Cov.: 33

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.858

GnomAD4 exome AF: 0.889 AC: 13231 AN: 14884 Hom.: 5882 Cov.: 0 AF XY: 0.892 AC XY: 6306 AN XY: 7066

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.889 AC: 13064 AN: 14696

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.869 AC: 73 AN: 84

Other (OTH) AF: 0.922 AC: 83 AN: 90

GnomAD4 genome AF: 0.855 AC: 130160 AN: 152240 Hom.: 55824 Cov.: 33 AF XY: 0.859 AC XY: 63961 AN XY: 74434

African (AFR) AF: 0.873 AC: 36277 AN: 41540

American (AMR) AF: 0.872 AC: 13332 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2584 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5170 AN: 5176

South Asian (SAS) AF: 0.929 AC: 4476 AN: 4820

European-Finnish (FIN) AF: 0.886 AC: 9400 AN: 10604

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56186 AN: 68018

Other (OTH) AF: 0.859 AC: 1813 AN: 2110

Alfa AF: 0.836 Hom.: 72207

Bravo AF: 0.857

Asia WGS AF: 0.955 AC: 3318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs346070; hg19: chr3-11303874;