3-11262188-T-C

Position:

• chr3-11262188-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH1	NM_001098212.2	c.*1687T>C		3_prime_UTR_variant	2/2	ENST00000431010.3	NP_001091682.1
HRH1	NM_000861.3	c.*1687T>C		3_prime_UTR_variant	3/3		NP_000852.1
HRH1	NM_001098211.2	c.*1687T>C		3_prime_UTR_variant	2/2		NP_001091681.1
HRH1	NM_001098213.2	c.*1687T>C		3_prime_UTR_variant	2/2		NP_001091683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRH1	ENST00000431010.3	c.*1687T>C		3_prime_UTR_variant	2/2	1	NM_001098212.2	ENSP00000397028.2
HRH1	ENST00000397056.1	c.*1687T>C		3_prime_UTR_variant	3/3	1		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

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.889

Gnomad4 NFE exome AF: 0.869

Gnomad4 OTH exome AF: 0.922

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

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.929

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.859

Alfa AF: 0.832 Hom.: 55767

Bravo AF: 0.857

Asia WGS AF: 0.955 AC: 3318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs346070; hg19: chr3-11303874;