18-24464436-G-T

Position:

• chr18-24464436-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.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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH4	NM_021624.4	c.193+3515G>T		intron_variant		ENST00000256906.5	NP_067637.2
HRH4	NM_001143828.2	c.193+3515G>T		intron_variant			NP_001137300.1
HRH4	NM_001160166.2	c.193+3515G>T		intron_variant			NP_001153638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRH4	ENST00000256906.5	c.193+3515G>T		intron_variant		1	NM_021624.4	ENSP00000256906	P1
HRH4	ENST00000426880.2	c.193+3515G>T		intron_variant		1		ENSP00000402526

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

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.734

Alfa AF: 0.757 Hom.: 43900

Bravo AF: 0.717

Asia WGS AF: 0.670 AC: 2329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.95
DANN	Benign	0.50

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: rs4483927; hg19: chr18-22044400;