Variant chr20-62216546-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_007232.3(HRH3):c.798C>T(p.His266His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000523 in 1,603,036 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 1 hom. )

Consequence

HRH3
NM_007232.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.39

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 Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 20-62216546-G-A is Benign according to our data. Variant chr20-62216546-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2672885.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.39 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH3	NM_007232.3 linkuse as main transcript	c.798C>T	p.His266His	synonymous_variant	3/3	ENST00000340177.10	NP_009163.2	Q9Y5N1-1
HRH3	XM_005260266.4 linkuse as main transcript	c.798C>T	p.His266His	synonymous_variant	3/4		XP_005260323.1	Q9Y5N1-2
HRH3	XM_017027623.2 linkuse as main transcript	c.756C>T	p.His252His	synonymous_variant	3/4		XP_016883112.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRH3	ENST00000340177.10 linkuse as main transcript	c.798C>T	p.His266His	synonymous_variant	3/3	1	NM_007232.3	ENSP00000342560.5		Q9Y5N1-1
HRH3	ENST00000317393.10 linkuse as main transcript	c.798C>T	p.His266His	synonymous_variant	3/5	1		ENSP00000321482.7		A0A0A0MR48

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000858

AC:

193

AN:

225004

Hom.:

AF XY:

0.000836

AC XY:

104

AN XY:

124440

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000681

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000386

Gnomad OTH exome

AF:

0.00126

GnomAD4 exome

AF:

0.000516

AC:

749

AN:

1450778

Hom.:

Cov.:

AF XY:

0.000542

AC XY:

391

AN XY:

720912

show subpopulations

Gnomad4 AFR exome

AF:

0.0000904

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0148

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000703

Gnomad4 FIN exome

AF:

0.0000199

Gnomad4 NFE exome

AF:

0.000256

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.000591

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.000536

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

HRH3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.058

DANN

Benign

0.56

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over