rs2067474

chr5-175682216-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

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 = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HRH2	NM_001367711.1	c.-525-493G>A		intron_variant		ENST00000636584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRH2	ENST00000636584.2	c.-525-493G>A		intron_variant		3	NM_001367711.1	P1
HRH2	ENST00000377291.2	c.-525-493G>A		intron_variant		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

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0495

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0964

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0772

Alfa AF: 0.0465 Hom.: 341

Bravo AF: 0.0891

Asia WGS AF: 0.108 AC: 378 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	0.11
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2067474; hg19: chr5-175109219;