18-24463389-T-C

Variant names:

• chr18-24463389-T-C
• rs623590
• NM_021624.4:c.193+2468T>C

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+2468T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 152,282 control chromosomes in the GnomAD database, including 59,604 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 0.88 (59604 hom., cov: 33)
• Consequence: HRH4 NM_021624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• 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 = 0.924 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH4	NM_021624.4	MANE Select	c.193+2468T>C		intron	N/A	NP_067637.2
	HRH4	NM_001143828.2		c.193+2468T>C		intron	N/A	NP_001137300.1	Q9H3N8-2
	HRH4	NM_001160166.2		c.193+2468T>C		intron	N/A	NP_001153638.1	B2KJ49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH4	ENST00000256906.5	TSL:1 MANE Select	c.193+2468T>C		intron	N/A	ENSP00000256906.4	Q9H3N8-1
	HRH4	ENST00000426880.2	TSL:1	c.193+2468T>C		intron	N/A	ENSP00000402526.2	Q9H3N8-2

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134209 AN: 152164 Hom.: 59553 Cov.: 33

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.888

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

GnomAD4 genome AF: 0.882 AC: 134321 AN: 152282 Hom.: 59604 Cov.: 33 AF XY: 0.882 AC XY: 65699 AN XY: 74452

African (AFR) AF: 0.807 AC: 33523 AN: 41538

American (AMR) AF: 0.937 AC: 14338 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3254 AN: 3472

East Asian (EAS) AF: 0.673 AC: 3490 AN: 5184

South Asian (SAS) AF: 0.868 AC: 4186 AN: 4820

European-Finnish (FIN) AF: 0.931 AC: 9894 AN: 10624

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62674 AN: 68026

Other (OTH) AF: 0.884 AC: 1867 AN: 2112

Alfa AF: 0.902 Hom.: 7687

Bravo AF: 0.879

Asia WGS AF: 0.764 AC: 2657 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.53
PhyloP100		-2.8
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: rs623590; hg19: chr18-22043353;