18-24464436-G-T

Variant names:

• chr18-24464436-G-T
• rs4483927
• NM_021624.4:c.193+3515G>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.193+3515G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 151,972 control chromosomes in the GnomAD database, including 39,801 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 0.72 (39801 hom., cov: 31)
• Consequence: HRH4 NM_021624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.761 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.193+3515G>T		intron	N/A	NP_067637.2
	HRH4	NM_001143828.2		c.193+3515G>T		intron	N/A	NP_001137300.1
	HRH4	NM_001160166.2		c.193+3515G>T		intron	N/A	NP_001153638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH4	ENST00000256906.5	TSL:1 MANE Select	c.193+3515G>T		intron	N/A	ENSP00000256906.4
	HRH4	ENST00000426880.2	TSL:1	c.193+3515G>T		intron	N/A	ENSP00000402526.2

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109207 AN: 151854 Hom.: 39770 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.737

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.719 AC: 109291 AN: 151972 Hom.: 39801 Cov.: 31 AF XY: 0.717 AC XY: 53277 AN XY: 74296

African (AFR) AF: 0.622 AC: 25741 AN: 41398

American (AMR) AF: 0.773 AC: 11804 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2763 AN: 3468

East Asian (EAS) AF: 0.639 AC: 3303 AN: 5170

South Asian (SAS) AF: 0.733 AC: 3539 AN: 4828

European-Finnish (FIN) AF: 0.757 AC: 7977 AN: 10544

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51630 AN: 67978

Other (OTH) AF: 0.734 AC: 1550 AN: 2112

Alfa AF: 0.744 Hom.: 119029

Bravo AF: 0.717

Asia WGS AF: 0.670 AC: 2329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.95
DANN	Benign	0.50
PhyloP100		-0.12
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: rs4483927; hg19: chr18-22044400;