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GeneBe

20-62219725-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_007232.3(HRH3):c.246C>T(p.Leu82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,597,186 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 72 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 62 hom. )

Consequence

HRH3
NM_007232.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.325
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-62219725-G-A is Benign according to our data. Variant chr20-62219725-G-A is described in ClinVar as [Benign]. Clinvar id is 769099.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.325 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HRH3NM_007232.3 linkuse as main transcriptc.246C>T p.Leu82= synonymous_variant 1/3 ENST00000340177.10
HRH3XM_005260266.4 linkuse as main transcriptc.246C>T p.Leu82= synonymous_variant 1/4
HRH3XM_017027623.2 linkuse as main transcriptc.246C>T p.Leu82= synonymous_variant 1/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HRH3ENST00000340177.10 linkuse as main transcriptc.246C>T p.Leu82= synonymous_variant 1/31 NM_007232.3 P1Q9Y5N1-1
HRH3ENST00000317393.10 linkuse as main transcriptc.246C>T p.Leu82= synonymous_variant 1/51

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0167
AC:
2541
AN:
152122
Hom.:
72
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0569
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00798
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.00410
AC:
988
AN:
241184
Hom.:
23
AF XY:
0.00299
AC XY:
393
AN XY:
131276
show subpopulations
Gnomad AFR exome
AF:
0.0549
Gnomad AMR exome
AF:
0.00280
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000684
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000385
Gnomad OTH exome
AF:
0.00206
GnomAD4 exome
AF:
0.00175
AC:
2534
AN:
1444946
Hom.:
62
Cov.:
31
AF XY:
0.00150
AC XY:
1075
AN XY:
718952
show subpopulations
Gnomad4 AFR exome
AF:
0.0581
Gnomad4 AMR exome
AF:
0.00322
Gnomad4 ASJ exome
AF:
0.0000391
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000827
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000225
Gnomad4 OTH exome
AF:
0.00400
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0167
AC:
2543
AN:
152240
Hom.:
72
Cov.:
32
AF XY:
0.0161
AC XY:
1198
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0568
Gnomad4 AMR
AF:
0.00791
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.00593
Hom.:
10
Bravo
AF:
0.0191
Asia WGS
AF:
0.00433
AC:
15
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
18
Dann
Benign
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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.

Other links and lift over

dbSNP: rs114303636; hg19: chr20-60794781; COSMIC: COSV58048406; API