dbSNP rs7651620: HRH1:p.Gly270Glu (chr3-11259846-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001098212.2(HRH1):c.809G>A(p.Gly270Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,614,006 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.014 ( 56 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 63 hom. )

Consequence

HRH1
NM_001098212.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.451

Publications

9 publications found

Variant links:

Genes affected

HRH1 (HGNC:5182): (histamine receptor H1) 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. The protein encoded by this gene is an integral membrane protein and belongs to the G protein-coupled receptor superfamily. It mediates the contraction of smooth muscles, the increase in capillary permeability due to contraction of terminal venules, the release of catecholamine from adrenal medulla, and neurotransmission in the central nervous system. It has been associated with multiple processes, including memory and learning, circadian rhythm, and thermoregulation. It is also known to contribute to the pathophysiology of allergic diseases such as atopic dermatitis, asthma, anaphylaxis and allergic rhinitis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2015]

HRH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0022179484).

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
HRH1	NM_001098212.2 link	c.809G>A	p.Gly270Glu	missense_variant	Exon 2 of 2	ENST00000431010.3	NP_001091682.1
HRH1	NM_000861.3 link	c.809G>A	p.Gly270Glu	missense_variant	Exon 3 of 3		NP_000852.1
HRH1	NM_001098211.2 link	c.809G>A	p.Gly270Glu	missense_variant	Exon 2 of 2		NP_001091681.1
HRH1	NM_001098213.2 link	c.809G>A	p.Gly270Glu	missense_variant	Exon 2 of 2		NP_001091683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
HRH1	ENST00000431010.3 link	c.809G>A	p.Gly270Glu	missense_variant	Exon 2 of 2	1	NM_001098212.2	ENSP00000397028.2
HRH1	ENST00000397056.1 link	c.809G>A	p.Gly270Glu	missense_variant	Exon 3 of 3	1		ENSP00000380247.1
HRH1	ENST00000438284.2 link	c.809G>A	p.Gly270Glu	missense_variant	Exon 2 of 2	2		ENSP00000406705.2

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2174

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00910

GnomAD2 exomes

AF:

0.00383

AC:

961

AN:

250874

AF XY:

0.00279

show subpopulations

Gnomad AFR exome

AF:

0.0530

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00153

AC:

2243

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

941

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.0545

AC:

1824

AN:

33480

American (AMR)

AF:

0.00266

AC:

119

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000151

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000683

AC:

AN:

1111984

Other (OTH)

AF:

0.00331

AC:

200

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

126

252

379

505

631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0143

AC:

2178

AN:

152218

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

1000

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0500

AC:

2076

AN:

41518

American (AMR)

AF:

0.00484

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68016

Other (OTH)

AF:

0.00900

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

102

204

305

407

509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00496

Hom.:

Bravo

AF:

0.0160

ESP6500AA

AF:

0.0474

AC:

209

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00450

AC:

546

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.6

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.57

.;.;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L

PhyloP100

0.45

PrimateAI

Benign

0.25

PROVEAN

Benign

0.45

N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.11

MVP

0.62

MPC

0.34

ClinPred

0.0022

GERP RS

-2.8

Varity_R

0.022

gMVP

0.14

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over