Variant chr20-62216366-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007232.3(HRH3):c.978G>A(p.Pro326Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,571,248 control chromosomes in the GnomAD database, including 17,014 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 0.15 ( 1897 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15117 hom. )

Consequence

HRH3
NM_007232.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.51

Variant links:

Genes affected

HRH3 (HGNC:5184): (histamine receptor H3) 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. This gene encodes one of the histamine receptors (H3) which belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and can regulate neurotransmitter release. This receptor can also increase voltage-dependent calcium current in smooth muscles and innervates the blood vessels and the heart in cardiovascular system. [provided by RefSeq, Jul 2008]

HRH3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026603937).

BP7

Synonymous conserved (PhyloP=-4.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH3	NM_007232.3 link	c.978G>A	p.Pro326Pro	synonymous_variant	3/3	ENST00000340177.10	NP_009163.2	Q9Y5N1-1
HRH3	XM_005260266.4 link	c.978G>A	p.Pro326Pro	synonymous_variant	3/4		XP_005260323.1	Q9Y5N1-2
HRH3	XM_017027623.2 link	c.936G>A	p.Pro312Pro	synonymous_variant	3/4		XP_016883112.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRH3	ENST00000340177.10 link	c.978G>A	p.Pro326Pro	synonymous_variant	3/3	1	NM_007232.3	ENSP00000342560.5		Q9Y5N1-1
HRH3	ENST00000317393.10 link	c.822-84G>A		intron_variant		1		ENSP00000321482.7		A0A0A0MR48

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23422

AN:

152110

Hom.:

1890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.0971

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.158

AC:

29378

AN:

185610

Hom.:

2298

AF XY:

0.160

AC XY:

16081

AN XY:

100444

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.0981

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.144

AC:

205004

AN:

1419020

Hom.:

15117

Cov.:

AF XY:

0.146

AC XY:

102467

AN XY:

701328

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.0991

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.154

AC:

23459

AN:

152228

Hom.:

1897

Cov.:

AF XY:

0.156

AC XY:

11574

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.0971

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.135

Hom.:

1200

Bravo

AF:

0.155

TwinsUK

AF:

0.142

AC:

527

ALSPAC

AF:

0.144

AC:

556

ESP6500AA

AF:

0.179

AC:

787

ESP6500EA

AF:

0.143

AC:

1221

ExAC

AF:

0.137

AC:

16191

Asia WGS

AF:

0.183

AC:

636

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.088

DANN

Benign

0.76

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0027

Sift4G

Pathogenic

0.0

Vest4

0.10

GERP RS

-9.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over