chr5-175683370-A-C

Variant names:

• chr5-175683370-A-C
• rs79385261
• NM_001367711.1:c.137A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367711.1(HRH2):​c.137A>C​(p.Asn46Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HRH2 NM_001367711.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 4 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20236802).

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.137A>C	p.Asn46Thr	missense	Exon 2 of 3	NP_001354640.1	A0A1B0GTK7
	HRH2	NM_001393460.1		c.137A>C	p.Asn46Thr	missense	Exon 3 of 4	NP_001380389.1	A0A1B0GTK7
	HRH2	NM_001393461.1		c.137A>C	p.Asn46Thr	missense	Exon 4 of 5	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.137A>C	p.Asn46Thr	missense	Exon 2 of 3	ENSP00000489742.1	A0A1B0GTK7
	HRH2	ENST00000377291.2	TSL:1	c.137A>C	p.Asn46Thr	missense	Exon 2 of 3	ENSP00000366506.2	P25021-2
	HRH2	ENST00000932189.1		c.137A>C	p.Asn46Thr	missense	Exon 3 of 4	ENSP00000602248.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251472 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.62	N
PhyloP100		2.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.11
Sift	Benign	0.26	T
Sift4G	Benign	0.44	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.57		Loss of sheet (P = 0.1158)
MVP		0.55
MPC		0.89
ClinPred		0.14	T
GERP RS		4.2
Varity_R		0.24
gMVP		0.29
Mutation Taster		=87/13	polymorphism

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: rs79385261; hg19: chr5-175110373;