rs16940762

Variant names:

• chr18-24465869-G-A
• rs16940762
• NM_021624.4:c.194-2919G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021624.4(HRH4):​c.194-2919G>A 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 152,066 control chromosomes in the GnomAD database, including 992 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 0.11 (992 hom., cov: 31)
• Consequence: HRH4 NM_021624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRH4	NM_021624.4	c.194-2919G>A		intron_variant	Intron 1 of 2	ENST00000256906.5	NP_067637.2
HRH4	NM_001143828.2	c.193+4948G>A		intron_variant	Intron 1 of 1		NP_001137300.1
HRH4	NM_001160166.2	c.193+4948G>A		intron_variant	Intron 1 of 1		NP_001153638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HRH4	ENST00000256906.5	c.194-2919G>A		intron_variant	Intron 1 of 2	1	NM_021624.4	ENSP00000256906.4
HRH4	ENST00000426880.2	c.193+4948G>A		intron_variant	Intron 1 of 1	1		ENSP00000402526.2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15956 AN: 151948 Hom.: 987 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.105 AC: 15980 AN: 152066 Hom.: 992 Cov.: 31 AF XY: 0.100 AC XY: 7452 AN XY: 74310

African (AFR) AF: 0.177 AC: 7318 AN: 41438

American (AMR) AF: 0.0635 AC: 971 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0289 AC: 139 AN: 4818

European-Finnish (FIN) AF: 0.0780 AC: 825 AN: 10572

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6156 AN: 67992

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.0994 Hom.: 161

Bravo AF: 0.108

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.61
PhyloP100		0.063
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: rs16940762; hg19: chr18-22045833;