chr3-11259021-T-C

Variant names:

• chr3-11259021-T-C
• rs901865
• NM_001098212.2:c.-17T>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.-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
• Publications: 30 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH1	NM_001098212.2	MANE Select	c.-17T>C		5_prime_UTR	Exon 2 of 2	NP_001091682.1	P35367
	HRH1	NM_000861.3		c.-17T>C		5_prime_UTR	Exon 3 of 3	NP_000852.1	P35367
	HRH1	NM_001098211.2		c.-17T>C		5_prime_UTR	Exon 2 of 2	NP_001091681.1	P35367

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH1	ENST00000431010.3	TSL:1 MANE Select	c.-17T>C		5_prime_UTR	Exon 2 of 2	ENSP00000397028.2	P35367
	HRH1	ENST00000397056.1	TSL:1	c.-17T>C		5_prime_UTR	Exon 3 of 3	ENSP00000380247.1	P35367
	HRH1	ENST00000438284.2	TSL:2	c.-17T>C		5_prime_UTR	Exon 2 of 2	ENSP00000406705.2	P35367

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

GnomAD2 exomes AF: 0.847 AC: 179794 AN: 212310 AF XY: 0.849

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 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

African (AFR) AF: 0.681 AC: 21840 AN: 32052

American (AMR) AF: 0.897 AC: 33710 AN: 37594

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 16877 AN: 22310

East Asian (EAS) AF: 0.940 AC: 36950 AN: 39292

South Asian (SAS) AF: 0.913 AC: 71402 AN: 78206

European-Finnish (FIN) AF: 0.877 AC: 45233 AN: 51590

Middle Eastern (MID) AF: 0.799 AC: 4389 AN: 5490

European-Non Finnish (NFE) AF: 0.827 AC: 897672 AN: 1085912

Other (OTH) AF: 0.826 AC: 47966 AN: 58094

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

African (AFR) AF: 0.688 AC: 28520 AN: 41430

American (AMR) AF: 0.851 AC: 13015 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2579 AN: 3470

East Asian (EAS) AF: 0.929 AC: 4798 AN: 5162

South Asian (SAS) AF: 0.920 AC: 4427 AN: 4814

European-Finnish (FIN) AF: 0.886 AC: 9380 AN: 10590

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56096 AN: 67982

Other (OTH) AF: 0.823 AC: 1739 AN: 2114

Alfa AF: 0.818 Hom.: 156998

Bravo AF: 0.793

Asia WGS AF: 0.911 AC: 3164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		0.52
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

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