rs16940765

Positions:

• chr18-24468583-T-C

Variant summary

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

The NM_021624.4(HRH4):​c.194-205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,274 control chromosomes in the GnomAD database, including 993 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 0.10 (993 hom., cov: 32)
• Consequence: HRH4 NM_021624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HRH4	NM_021624.4	c.194-205T>C		intron_variant		ENST00000256906.5
HRH4	NM_001143828.2	c.193+7662T>C		intron_variant
HRH4	NM_001160166.2	c.193+7662T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRH4	ENST00000256906.5	c.194-205T>C		intron_variant		1	NM_021624.4	P1
HRH4	ENST00000426880.2	c.193+7662T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15938 AN: 152156 Hom.: 988 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0955

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

GnomAD4 genome AF: 0.105 AC: 15962 AN: 152274 Hom.: 993 Cov.: 32 AF XY: 0.100 AC XY: 7463 AN XY: 74474

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.000577

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.0907

Gnomad4 OTH AF: 0.0945

Alfa AF: 0.0900 Hom.: 939

Bravo AF: 0.108

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.7
DANN	Benign	0.29

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: rs16940765; hg19: chr18-22048547;