rs17187619

Positions:

• chr18-24469616-T-C
• chr18-24469616-T-G

Variant summary

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

The NM_021624.4(HRH4):​c.357+665T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,100 control chromosomes in the GnomAD database, including 3,702 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 0.21 (3702 hom., cov: 32)
• Consequence: HRH4 NM_021624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HRH4	NM_021624.4	c.357+665T>C		intron_variant		ENST00000256906.5
HRH4	NM_001143828.2	c.194-7231T>C		intron_variant
HRH4	NM_001160166.2	c.194-7131T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRH4	ENST00000256906.5	c.357+665T>C		intron_variant		1	NM_021624.4	P1
HRH4	ENST00000426880.2	c.194-7231T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31599 AN: 151982 Hom.: 3690 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.208 AC: 31643 AN: 152100 Hom.: 3702 Cov.: 32 AF XY: 0.212 AC XY: 15751 AN XY: 74344

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.233

Alfa AF: 0.211 Hom.: 1391

Bravo AF: 0.213

Asia WGS AF: 0.211 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.7
DANN	Benign	0.87

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: rs17187619; hg19: chr18-22049580;