rs17187619

Variant names:

• chr18-24469616-T-C
• rs17187619
• NM_021624.4:c.357+665T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 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.357+665T>C		intron	N/A	NP_067637.2
	HRH4	NM_001143828.2		c.194-7231T>C		intron	N/A	NP_001137300.1
	HRH4	NM_001160166.2		c.194-7131T>C		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.357+665T>C		intron	N/A	ENSP00000256906.4
	HRH4	ENST00000426880.2	TSL:1	c.194-7231T>C		intron	N/A	ENSP00000402526.2

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

African (AFR) AF: 0.122 AC: 5053 AN: 41506

American (AMR) AF: 0.333 AC: 5078 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 866 AN: 3470

East Asian (EAS) AF: 0.183 AC: 944 AN: 5172

South Asian (SAS) AF: 0.231 AC: 1114 AN: 4818

European-Finnish (FIN) AF: 0.266 AC: 2816 AN: 10580

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 14993 AN: 67976

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.212 Hom.: 2283

Bravo AF: 0.213

Asia WGS AF: 0.211 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.7
DANN	Benign	0.87
PhyloP100		0.16
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: rs17187619; hg19: chr18-22049580;