rs2067474

Variant names:

• chr5-175682216-G-A
• rs2067474
• NM_001367711.1:c.-525-493G>A

Variant summary

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

The NM_001367711.1(HRH2):​c.-525-493G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 152,256 control chromosomes in the GnomAD database, including 896 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 0.083 (896 hom., cov: 33)
• Consequence: HRH2 NM_001367711.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 11 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 -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 = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367711.1. 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
	HRH2	NM_001367711.1	MANE Select	c.-525-493G>A		intron	N/A	NP_001354640.1	A0A1B0GTK7
	HRH2	NM_001393460.1		c.-525-493G>A		intron	N/A	NP_001380389.1	A0A1B0GTK7
	HRH2	NM_001393461.1		c.-525-493G>A		intron	N/A	NP_001380390.1	A0A1B0GTK7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH2	ENST00000636584.2	TSL:3 MANE Select	c.-525-493G>A		intron	N/A	ENSP00000489742.1	A0A1B0GTK7
	HRH2	ENST00000377291.2	TSL:1	c.-525-493G>A		intron	N/A	ENSP00000366506.2	P25021-2
	HRH2	ENST00000932189.1		c.-525-493G>A		intron	N/A	ENSP00000602248.1

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12565 AN: 152138 Hom.: 887 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0496

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.0827 AC: 12590 AN: 152256 Hom.: 896 Cov.: 33 AF XY: 0.0831 AC XY: 6191 AN XY: 74472

African (AFR) AF: 0.179 AC: 7455 AN: 41544

American (AMR) AF: 0.0495 AC: 757 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.152 AC: 789 AN: 5174

South Asian (SAS) AF: 0.0964 AC: 465 AN: 4822

European-Finnish (FIN) AF: 0.0420 AC: 446 AN: 10620

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0345 AC: 2345 AN: 68014

Other (OTH) AF: 0.0772 AC: 163 AN: 2112

Alfa AF: 0.0523 Hom.: 1079

Bravo AF: 0.0891

Asia WGS AF: 0.108 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.78
PhyloP100		-1.1
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2067474; hg19: chr5-175109219;