Genetic Variant HTR3B:p.Ala154Ala (chr11-113932382-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006028.5(HTR3B):c.462G>A(p.Ala154Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 1,613,556 control chromosomes in the GnomAD database, including 3,860 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 0.059 ( 639 hom., cov: 33)

Exomes 𝑓: 0.027 ( 3221 hom. )

Consequence

HTR3B
NM_006028.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

17 publications found

Variant links:

Genes affected

HTR3B (HGNC:5298): (5-hydroxytryptamine receptor 3B) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit B of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. It is not functional as a homomeric complex, but a pentaheteromeric complex with subunit A (HTR3A) displays the full functional features of this receptor. [provided by RefSeq, Aug 2011]

HTR3B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.016).

BP7

Synonymous conserved (PhyloP=-2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3B	NM_006028.5 link	c.462G>A	p.Ala154Ala	synonymous_variant	Exon 5 of 9	ENST00000260191.8	NP_006019.1	O95264-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTR3B	ENST00000260191.8 link	c.462G>A	p.Ala154Ala	synonymous_variant	Exon 5 of 9	1	NM_006028.5	ENSP00000260191.2	O95264-1
HTR3B	ENST00000537778.5 link	c.429G>A	p.Ala143Ala	synonymous_variant	Exon 4 of 8	1		ENSP00000443118.1	O95264-2
HTR3B	ENST00000543092.1 link	c.246G>A	p.Ala82Ala	synonymous_variant	Exon 3 of 5	3		ENSP00000440894.1	H0YFX8

Frequencies

GnomAD3 genomes

AF:

0.0591

AC:

8982

AN:

152088

Hom.:

631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0996

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.0682

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00895

Gnomad OTH

AF:

0.0589

GnomAD2 exomes

AF:

0.0773

AC:

19437

AN:

251290

AF XY:

0.0663

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.00578

Gnomad NFE exome

AF:

0.00750

Gnomad OTH exome

AF:

0.0506

GnomAD4 exome

AF:

0.0271

AC:

39631

AN:

1461350

Hom.:

3221

Cov.:

AF XY:

0.0266

AC XY:

19373

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.0966

AC:

3232

AN:

33448

American (AMR)

AF:

0.242

AC:

10813

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

368

AN:

26136

East Asian (EAS)

AF:

0.232

AC:

9214

AN:

39690

South Asian (SAS)

AF:

0.0538

AC:

4640

AN:

86238

European-Finnish (FIN)

AF:

0.00524

AC:

280

AN:

53410

Middle Eastern (MID)

AF:

0.0272

AC:

157

AN:

5766

European-Non Finnish (NFE)

AF:

0.00749

AC:

8328

AN:

1111612

Other (OTH)

AF:

0.0431

AC:

2599

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

1658

3316

4975

6633

8291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.0592

AC:

9016

AN:

152206

Hom.:

639

Cov.:

AF XY:

0.0614

AC XY:

4569

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0996

AC:

4133

AN:

41498

American (AMR)

AF:

0.143

AC:

2183

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.291

AC:

1505

AN:

5174

South Asian (SAS)

AF:

0.0680

AC:

328

AN:

4820

European-Finnish (FIN)

AF:

0.00631

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00897

AC:

610

AN:

68024

Other (OTH)

AF:

0.0645

AC:

136

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

400

800

1199

1599

1999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0317

Hom.:

723

Bravo

AF:

0.0756

EpiCase

AF:

0.00873

EpiControl

AF:

0.00788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.1

(source)

DANN

Benign

0.41

PhyloP100

-2.0

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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