rs1434620794

Variant names:

• chr18-24468938-C-G
• rs1434620794
• NM_021624.4:c.344C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-24468938-C-G
• chr18-24468938-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_021624.4(HRH4):​c.344C>G​(p.Ser115*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,500 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (1 hom.)
• Consequence: HRH4 NM_021624.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.344C>G	p.Ser115*	stop_gained	Exon 2 of 3	NP_067637.2
	HRH4	NM_001143828.2		c.194-7909C>G		intron	N/A	NP_001137300.1	Q9H3N8-2
	HRH4	NM_001160166.2		c.194-7809C>G		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.344C>G	p.Ser115*	stop_gained	Exon 2 of 3	ENSP00000256906.4	Q9H3N8-1
	HRH4	ENST00000426880.2	TSL:1	c.194-7909C>G		intron	N/A	ENSP00000402526.2	Q9H3N8-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1452500 Hom.: 1 Cov.: 29 AF XY: 0.00000277 AC XY: 2 AN XY: 722174

African (AFR) AF: 0.00 AC: 0 AN: 33092

American (AMR) AF: 0.00 AC: 0 AN: 42952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39244

South Asian (SAS) AF: 0.0000355 AC: 3 AN: 84502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107708

Other (OTH) AF: 0.00 AC: 0 AN: 60050

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		3.5
Vest4		0.97
GERP RS		3.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.63		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.63		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1434620794; hg19: chr18-22048902;