rs1421125

Positions:

• chr18-24477947-G-T

Variant summary

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

The NM_021624.4(HRH4):​c.*385G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 161,962 control chromosomes in the GnomAD database, including 8,716 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 0.31 (8090 hom., cov: 34)
  • Exomes 𝑓: 0.34 (626 hom.)
• Consequence: HRH4 NM_021624.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.867

Genes affected

HRH4 (HGNC:17383): (histamine receptor H4) Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by a family of histamine receptors, which are a subset of the G-protein coupled receptor superfamily. This gene encodes a histamine receptor that is predominantly expressed in haematopoietic cells. The protein is thought to play a role in inflammation and allergy reponses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH4	NM_021624.4	c.*385G>T		3_prime_UTR_variant	3/3	ENST00000256906.5	NP_067637.2
HRH4	NM_001143828.2	c.*385G>T		3_prime_UTR_variant	2/2		NP_001137300.1
HRH4	NM_001160166.2	c.*1190G>T		3_prime_UTR_variant	2/2		NP_001153638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRH4	ENST00000256906.5	c.*385G>T		3_prime_UTR_variant	3/3	1	NM_021624.4	ENSP00000256906	P1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47667 AN: 152096 Hom.: 8092 Cov.: 34

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.344 AC: 3352 AN: 9746 Hom.: 626 Cov.: 0 AF XY: 0.348 AC XY: 1823 AN XY: 5240

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.0788

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.383

GnomAD4 genome AF: 0.313 AC: 47665 AN: 152216 Hom.: 8090 Cov.: 34 AF XY: 0.309 AC XY: 23015 AN XY: 74412

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.337

Alfa AF: 0.375 Hom.: 18534

Bravo AF: 0.302

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.61

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: rs1421125; hg19: chr18-22057911;