rs2276305

Variant names:

• chr11-113932382-G-A
• rs2276305
• NM_006028.5:c.462G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-113932382-G-A
• chr11-113932382-G-C
• chr11-113932382-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 17 publications found

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

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	c.462G>A	p.Ala154Ala	synonymous_variant	Exon 5 of 9	ENST00000260191.8	NP_006019.1

Ensembl

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

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

GnomAD2 exomes AF: 0.0773 AC: 19437 AN: 251290 AF XY: 0.0663

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

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

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

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: 47 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: 67 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00897 AC: 610 AN: 68024

Other (OTH) AF: 0.0645 AC: 136 AN: 2110

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
DANN	Benign	0.41
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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