chr18-24477947-G-T

Variant names:

• chr18-24477947-G-T
• rs1421125
• NM_021624.4:c.*385G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021624.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH4	NM_021624.4	MANE Select	c.*385G>T		3_prime_UTR	Exon 3 of 3	NP_067637.2
	HRH4	NM_001143828.2		c.*385G>T		3_prime_UTR	Exon 2 of 2	NP_001137300.1
	HRH4	NM_001160166.2		c.*1190G>T		3_prime_UTR	Exon 2 of 2	NP_001153638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH4	ENST00000256906.5	TSL:1 MANE Select	c.*385G>T		3_prime_UTR	Exon 3 of 3	ENSP00000256906.4

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

African (AFR) AF: 0.256 AC: 40 AN: 156

American (AMR) AF: 0.245 AC: 345 AN: 1410

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 90 AN: 196

East Asian (EAS) AF: 0.0788 AC: 32 AN: 406

South Asian (SAS) AF: 0.320 AC: 307 AN: 958

European-Finnish (FIN) AF: 0.264 AC: 48 AN: 182

Middle Eastern (MID) AF: 0.500 AC: 12 AN: 24

European-Non Finnish (NFE) AF: 0.387 AC: 2315 AN: 5988

Other (OTH) AF: 0.383 AC: 163 AN: 426

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

African (AFR) AF: 0.211 AC: 8750 AN: 41534

American (AMR) AF: 0.265 AC: 4050 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3472

East Asian (EAS) AF: 0.110 AC: 567 AN: 5178

South Asian (SAS) AF: 0.361 AC: 1744 AN: 4828

European-Finnish (FIN) AF: 0.315 AC: 3336 AN: 10588

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26506 AN: 68006

Other (OTH) AF: 0.337 AC: 712 AN: 2114

Alfa AF: 0.367 Hom.: 39170

Bravo AF: 0.302

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.61
PhyloP100		0.87
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: rs1421125; hg19: chr18-22057911;