chr3-11259079-G-A

Position:

chr3-11259079-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_001098212.2(HRH1):c.42G>A(p.Met14Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000872 in 1,611,990 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00082 ( 1 hom. )

Consequence

HRH1
NM_001098212.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.83

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006652117).

BP6

Variant 3-11259079-G-A is Benign according to our data. Variant chr3-11259079-G-A is described in ClinVar as [Benign]. Clinvar id is 733135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH1	NM_001098212.2 link	c.42G>A	p.Met14Ile	missense_variant	2/2	ENST00000431010.3	NP_001091682.1	P35367
HRH1	NM_000861.3 link	c.42G>A	p.Met14Ile	missense_variant	3/3		NP_000852.1	P35367
HRH1	NM_001098211.2 link	c.42G>A	p.Met14Ile	missense_variant	2/2		NP_001091681.1	P35367
HRH1	NM_001098213.2 link	c.42G>A	p.Met14Ile	missense_variant	2/2		NP_001091683.1	P35367

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HRH1	ENST00000431010.3 link	c.42G>A	p.Met14Ile	missense_variant	2/2	1	NM_001098212.2	ENSP00000397028.2	P35367
HRH1	ENST00000397056.1 link	c.42G>A	p.Met14Ile	missense_variant	3/3	1		ENSP00000380247.1	P35367
HRH1	ENST00000438284.2 link	c.42G>A	p.Met14Ile	missense_variant	2/2	2		ENSP00000406705.2	P35367
HRH1	ENST00000413416.1 link	c.*4G>A		downstream_gene_variant		4		ENSP00000392383.1	C9J2E6

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

215

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00120

AC:

297

AN:

248438

Hom.:

AF XY:

0.00108

AC XY:

145

AN XY:

134340

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000651

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.000815

AC:

1190

AN:

1459636

Hom.:

Cov.:

AF XY:

0.000812

AC XY:

590

AN XY:

726192

show subpopulations

Gnomad4 AFR exome

AF:

0.00177

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000508

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00141

AC:

215

AN:

152354

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00137

Hom.:

Bravo

AF:

0.00180

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000997

AC:

121

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

T;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.67

.;.;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.0067

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.95

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.058

T;T;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.95

P;P;P

Vest4

0.30

MutPred

0.43

Loss of disorder (P = 0.0211);Loss of disorder (P = 0.0211);Loss of disorder (P = 0.0211);

MVP

0.74

MPC

0.34

ClinPred

0.024

GERP RS

5.7

Varity_R

0.24

gMVP

0.51

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