rs1800689

Variant names:

• chr5-175683776-G-A
• rs1800689
• NM_001367711.1:c.543G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-175683776-G-A
• chr5-175683776-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000636584.2(HRH2):​c.543G>A​(p.Val181Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,614,128 control chromosomes in the GnomAD database, including 3,333 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 0.046 (238 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3095 hom.)
• Consequence: HRH2 ENST00000636584.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 14 publications found

Genes affected

HRH2 (HGNC:5183): (histamine receptor H2) Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. Histamine receptor H2 belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and stimulates gastric acid secretion. It also regulates gastrointestinal motility and intestinal secretion and is thought to be involved in regulating cell growth and differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0677 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636584.2. 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
	HRH2	NM_001367711.1	MANE Select	c.543G>A	p.Val181Val	synonymous	Exon 2 of 3	NP_001354640.1
	HRH2	NM_001393460.1		c.543G>A	p.Val181Val	synonymous	Exon 3 of 4	NP_001380389.1
	HRH2	NM_001393461.1		c.543G>A	p.Val181Val	synonymous	Exon 4 of 5	NP_001380390.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH2	ENST00000636584.2	TSL:3 MANE Select	c.543G>A	p.Val181Val	synonymous	Exon 2 of 3	ENSP00000489742.1
	HRH2	ENST00000377291.2	TSL:1	c.543G>A	p.Val181Val	synonymous	Exon 2 of 3	ENSP00000366506.2
	HRH2	ENST00000624694.2	TSL:5	n.543G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000490705.1

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7050 AN: 152122 Hom.: 237 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0489

GnomAD2 exomes AF: 0.0535 AC: 13462 AN: 251442 AF XY: 0.0555

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.0352

Gnomad ASJ exome AF: 0.0747

Gnomad EAS exome AF: 0.0517

Gnomad FIN exome AF: 0.0329

Gnomad NFE exome AF: 0.0617

Gnomad OTH exome AF: 0.0693

GnomAD4 exome AF: 0.0627 AC: 91697 AN: 1461886 Hom.: 3095 Cov.: 33 AF XY: 0.0638 AC XY: 46365 AN XY: 727240

African (AFR) AF: 0.00944 AC: 316 AN: 33480

American (AMR) AF: 0.0378 AC: 1690 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 1912 AN: 26136

East Asian (EAS) AF: 0.0436 AC: 1730 AN: 39700

South Asian (SAS) AF: 0.0745 AC: 6427 AN: 86258

European-Finnish (FIN) AF: 0.0328 AC: 1750 AN: 53420

Middle Eastern (MID) AF: 0.0747 AC: 431 AN: 5768

European-Non Finnish (NFE) AF: 0.0662 AC: 73601 AN: 1112004

Other (OTH) AF: 0.0636 AC: 3840 AN: 60396

GnomAD4 genome AF: 0.0463 AC: 7048 AN: 152242 Hom.: 238 Cov.: 32 AF XY: 0.0457 AC XY: 3399 AN XY: 74432

African (AFR) AF: 0.0110 AC: 455 AN: 41534

American (AMR) AF: 0.0553 AC: 846 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 259 AN: 3472

East Asian (EAS) AF: 0.0509 AC: 264 AN: 5184

South Asian (SAS) AF: 0.0740 AC: 357 AN: 4822

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0640 AC: 4350 AN: 68016

Other (OTH) AF: 0.0475 AC: 100 AN: 2106

Alfa AF: 0.0604 Hom.: 506

Bravo AF: 0.0454

Asia WGS AF: 0.0530 AC: 183 AN: 3478

EpiCase AF: 0.0667

EpiControl AF: 0.0672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.65
PhyloP100		-1.0
Mutation Taster		=95/5	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: rs1800689; hg19: chr5-175110779; COSMIC: COSV51574263;