18-24460771-C-A

Variant names:

• chr18-24460771-C-A
• NM_021624.4:c.43C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021624.4(HRH4):​c.43C>A​(p.Arg15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,388,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HRH4 NM_021624.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059534132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRH4	NM_021624.4	c.43C>A	p.Arg15Ser	missense_variant	Exon 1 of 3	ENST00000256906.5	NP_067637.2
HRH4	NM_001143828.2	c.43C>A	p.Arg15Ser	missense_variant	Exon 1 of 2		NP_001137300.1
HRH4	NM_001160166.2	c.43C>A	p.Arg15Ser	missense_variant	Exon 1 of 2		NP_001153638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HRH4	ENST00000256906.5	c.43C>A	p.Arg15Ser	missense_variant	Exon 1 of 3	1	NM_021624.4	ENSP00000256906.4
HRH4	ENST00000426880.2	c.43C>A	p.Arg15Ser	missense_variant	Exon 1 of 2	1		ENSP00000402526.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1388212 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 683104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.081
DANN	Benign	0.32
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.34	N;N
REVEL	Benign	0.039
Sift	Benign	0.80	T;T
Sift4G	Benign	0.78	T;T
Polyphen		0.0030	B;.
Vest4		0.14
MutPred		0.58		Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);
MVP		0.12
MPC		0.11
ClinPred		0.029	T
GERP RS		-7.9
Varity_R		0.10
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-22040735;