5-175693895-A-G

Position:

• chr5-175693895-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105377743 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HRH2	NM_001367711.1	c.1076+9586A>G		intron_variant		ENST00000636584.2
LOC105377743	XR_941267.3	n.2896T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRH2	ENST00000636584.2	c.1076+9586A>G		intron_variant		3	NM_001367711.1	P1
HRH2	ENST00000624694.2	c.*120+2536A>G		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0722

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.226

Alfa AF: 0.138 Hom.: 3646

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs632994; hg19: chr5-175120898;