rs2276305

chr11-113932382-G-Achr11-113932382-G-Cchr11-113932382-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006028.5(HTR3B):c.462G>A(p.Ala154=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• 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/exons	MANE	UniProt
HTR3B	NM_006028.5	c.462G>A	p.Ala154=	synonymous_variant	5/9	ENST00000260191.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3B	ENST00000260191.8	c.462G>A	p.Ala154=	synonymous_variant	5/9	1	NM_006028.5	P2
HTR3B	ENST00000537778.5	c.429G>A	p.Ala143=	synonymous_variant	4/8	1		A2
HTR3B	ENST00000543092.1	c.249G>A	p.Ala83=	synonymous_variant	3/5	3

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8982 AN: 152088 Hom.: 631 Cov.: 33

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

GnomAD3 exomes AF: 0.0773 AC: 19437 AN: 251290 Hom.: 2391 AF XY: 0.0663 AC XY: 9002 AN XY: 135806

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 SAS exome AF: 0.0553

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.: 32 AF XY: 0.0266 AC XY: 19373 AN XY: 727022

Gnomad4 AFR exome AF: 0.0966

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.0538

Gnomad4 FIN exome AF: 0.00524

Gnomad4 NFE exome AF: 0.00749

Gnomad4 OTH exome AF: 0.0431

GnomAD4 genome AF: 0.0592 AC: 9016 AN: 152206 Hom.: 639 Cov.: 33 AF XY: 0.0614 AC XY: 4569 AN XY: 74432

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.0680

Gnomad4 FIN AF: 0.00631

Gnomad4 NFE AF: 0.00897

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0232 Hom.: 384

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
Dann	Benign	0.41

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

Other links and lift over

dbSNP: rs2276305; hg19: chr11-113803104; COSMIC: COSV52745008;