rs13064530

chr3-11224228-G-A

Variant summary

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

The NM_001098212.2(HRH1):c.-35-34775G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,046 control chromosomes in the GnomAD database, including 4,603 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 0.24 (4603 hom., cov: 32)
• Consequence: HRH1 NM_001098212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HRH1	NM_001098212.2	c.-35-34775G>A		intron_variant		ENST00000431010.3
LOC102723663	XR_001740596.2	n.219+1472C>T		intron_variant, non_coding_transcript_variant
HRH1	NM_001098213.2	c.-35-34775G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRH1	ENST00000431010.3	c.-35-34775G>A		intron_variant		1	NM_001098212.2	P1
	ENST00000648436.1	n.178+1472C>T		intron_variant, non_coding_transcript_variant
HRH1	ENST00000438284.2	c.-35-34775G>A		intron_variant		2		P1
	ENST00000658562.1	n.144+1468C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37143 AN: 151928 Hom.: 4598 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.245 AC: 37180 AN: 152046 Hom.: 4603 Cov.: 32 AF XY: 0.243 AC XY: 18048 AN XY: 74326

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.234

Alfa AF: 0.233 Hom.: 533

Bravo AF: 0.244

Asia WGS AF: 0.349 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	3.3
Dann	Benign	0.83

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: rs13064530; hg19: chr3-11265914;