5-175693895-A-G

Variant names:

• chr5-175693895-A-G
• rs632994
• NM_001367711.1:c.1076+9586A>G

Variant summary

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

The NM_001367711.1(HRH2):​c.1076+9586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,970 control chromosomes in the GnomAD database, including 10,807 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 0.27 (10807 hom., cov: 32)
• Consequence: HRH2 NM_001367711.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 5 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]

ENSG00000306371 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRH2	NM_001367711.1	c.1076+9586A>G		intron_variant	Intron 2 of 2	ENST00000636584.2	NP_001354640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HRH2	ENST00000636584.2	c.1076+9586A>G		intron_variant	Intron 2 of 2	3	NM_001367711.1	ENSP00000489742.1
ENSG00000306371	ENST00000817287.1	n.184T>C		non_coding_transcript_exon_variant	Exon 2 of 2
HRH2	ENST00000624694.2	n.*120+2536A>G		intron_variant	Intron 2 of 2	5		ENSP00000490705.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41487 AN: 151852 Hom.: 10760 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0722

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.274 AC: 41588 AN: 151970 Hom.: 10807 Cov.: 32 AF XY: 0.269 AC XY: 19949 AN XY: 74290

African (AFR) AF: 0.682 AC: 28282 AN: 41442

American (AMR) AF: 0.168 AC: 2560 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3468

East Asian (EAS) AF: 0.204 AC: 1049 AN: 5152

South Asian (SAS) AF: 0.197 AC: 947 AN: 4806

European-Finnish (FIN) AF: 0.0722 AC: 763 AN: 10574

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.102 AC: 6953 AN: 67942

Other (OTH) AF: 0.226 AC: 477 AN: 2106

Alfa AF: 0.161 Hom.: 12660

Bravo AF: 0.299

Asia WGS AF: 0.208 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.015
DANN	Benign	0.54
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs632994; hg19: chr5-175120898;