3-11252624-T-C

Variant names:

• chr3-11252624-T-C
• rs346074
• NM_001098212.2:c.-35-6379T>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.-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
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 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.-35-6379T>C		intron	N/A	NP_001091682.1	P35367
	HRH1	NM_001098211.2		c.-35-6379T>C		intron	N/A	NP_001091681.1	P35367
	HRH1	NM_001098213.2		c.-35-6379T>C		intron	N/A	NP_001091683.1	P35367

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH1	ENST00000431010.3	TSL:1 MANE Select	c.-35-6379T>C		intron	N/A	ENSP00000397028.2	P35367
	HRH1	ENST00000903207.1		c.-630T>C		5_prime_UTR	Exon 1 of 2	ENSP00000573266.1
	HRH1	ENST00000438284.2	TSL:2	c.-35-6379T>C		intron	N/A	ENSP00000406705.2	P35367

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.352 AC: 14597 AN: 41440

American (AMR) AF: 0.485 AC: 7413 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1918 AN: 3466

East Asian (EAS) AF: 0.660 AC: 3414 AN: 5174

South Asian (SAS) AF: 0.525 AC: 2530 AN: 4822

European-Finnish (FIN) AF: 0.643 AC: 6785 AN: 10550

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44508 AN: 67952

Other (OTH) AF: 0.568 AC: 1202 AN: 2116

Alfa AF: 0.572 Hom.: 3985

Bravo AF: 0.530

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.49
PhyloP100		-0.97
PromoterAI		0.023	Neutral
Mutation Taster		=100/0	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: rs346074; hg19: chr3-11294310;