3-11259021-T-C

Variant names:

• chr3-11259021-T-C
• rs901865
• NM_001098212.2:c.-17T>C

Variant summary

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

The NM_001098212.2(HRH1):​c.-17T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 1,562,594 control chromosomes in the GnomAD database, including 540,701 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 0.80 (48934 hom., cov: 30)
  • Exomes 𝑓: 0.83 (491767 hom.)
• Consequence: HRH1 NM_001098212.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRH1	NM_001098212.2	c.-17T>C		5_prime_UTR_variant	Exon 2 of 2	ENST00000431010.3	NP_001091682.1
HRH1	NM_000861.3	c.-17T>C		5_prime_UTR_variant	Exon 3 of 3		NP_000852.1
HRH1	NM_001098211.2	c.-17T>C		5_prime_UTR_variant	Exon 2 of 2		NP_001091681.1
HRH1	NM_001098213.2	c.-17T>C		5_prime_UTR_variant	Exon 2 of 2		NP_001091683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HRH1	ENST00000431010	c.-17T>C		5_prime_UTR_variant	Exon 2 of 2	1	NM_001098212.2	ENSP00000397028.2
HRH1	ENST00000397056	c.-17T>C		5_prime_UTR_variant	Exon 3 of 3	1		ENSP00000380247.1
HRH1	ENST00000438284	c.-17T>C		5_prime_UTR_variant	Exon 2 of 2	2		ENSP00000406705.2
HRH1	ENST00000413416.1	c.-17T>C		5_prime_UTR_variant	Exon 2 of 2	4		ENSP00000392383.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121392 AN: 151936 Hom.: 48906 Cov.: 30

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.821

GnomAD3 exomes AF: 0.847 AC: 179794 AN: 212310 Hom.: 76667 AF XY: 0.849 AC XY: 96391 AN XY: 113520

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.901

Gnomad ASJ exome AF: 0.741

Gnomad EAS exome AF: 0.931

Gnomad SAS exome AF: 0.916

Gnomad FIN exome AF: 0.886

Gnomad NFE exome AF: 0.826

Gnomad OTH exome AF: 0.837

GnomAD4 exome AF: 0.834 AC: 1176039 AN: 1410540 Hom.: 491767 Cov.: 44 AF XY: 0.836 AC XY: 582447 AN XY: 696452

Gnomad4 AFR exome AF: 0.681

Gnomad4 AMR exome AF: 0.897

Gnomad4 ASJ exome AF: 0.756

Gnomad4 EAS exome AF: 0.940

Gnomad4 SAS exome AF: 0.913

Gnomad4 FIN exome AF: 0.877

Gnomad4 NFE exome AF: 0.827

Gnomad4 OTH exome AF: 0.826

GnomAD4 genome AF: 0.799 AC: 121473 AN: 152054 Hom.: 48934 Cov.: 30 AF XY: 0.805 AC XY: 59811 AN XY: 74328

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.823

Alfa AF: 0.821 Hom.: 71980

Bravo AF: 0.793

Asia WGS AF: 0.911 AC: 3164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.39

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: rs901865; hg19: chr3-11300707; COSMIC: COSV101229022;