3-11252624-T-C

Position:

• chr3-11252624-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.-35-6379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,996 control chromosomes in the GnomAD database, including 23,990 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 0.55 (23990 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: HRH1 NM_001098212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.968

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH1	NM_001098212.2	c.-35-6379T>C		intron_variant		ENST00000431010.3	NP_001091682.1
HRH1	NM_001098211.2	c.-35-6379T>C		intron_variant			NP_001091681.1
HRH1	NM_001098213.2	c.-35-6379T>C		intron_variant			NP_001091683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRH1	ENST00000431010.3	c.-35-6379T>C		intron_variant		1	NM_001098212.2	ENSP00000397028.2
HRH1	ENST00000438284.2	c.-35-6379T>C		intron_variant		2		ENSP00000406705.2
HRH1	ENST00000413416.1	c.-35-6379T>C		intron_variant		4		ENSP00000392383.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83030 AN: 151876 Hom.: 23986 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.564

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.546 AC: 83063 AN: 151994 Hom.: 23990 Cov.: 32 AF XY: 0.544 AC XY: 40398 AN XY: 74282

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.568

Alfa AF: 0.580 Hom.: 3934

Bravo AF: 0.530

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.49

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: rs346074; hg19: chr3-11294310;