rs17116138

Variant names:

• chr11-113932944-G-A
• rs17116138
• NM_006028.5:c.547G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006028.5(HTR3B):​c.547G>A​(p.Val183Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,613,786 control chromosomes in the GnomAD database, including 1,311 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.053 (276 hom., cov: 32)
  • Exomes 𝑓: 0.033 (1035 hom.)
• Consequence: HTR3B NM_006028.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644
• Publications: 23 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001542449).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006028.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3B	NM_006028.5	MANE Select	c.547G>A	p.Val183Ile	missense	Exon 6 of 9	NP_006019.1
	HTR3B	NM_001363563.2		c.514G>A	p.Val172Ile	missense	Exon 5 of 8	NP_001350492.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3B	ENST00000260191.8	TSL:1 MANE Select	c.547G>A	p.Val183Ile	missense	Exon 6 of 9	ENSP00000260191.2
	HTR3B	ENST00000537778.5	TSL:1	c.514G>A	p.Val172Ile	missense	Exon 5 of 8	ENSP00000443118.1
	HTR3B	ENST00000543092.1	TSL:3	c.331G>A	p.Val111Ile	missense	Exon 4 of 5	ENSP00000440894.1

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8055 AN: 152082 Hom.: 275 Cov.: 32

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.0469

GnomAD2 exomes AF: 0.0438 AC: 10992 AN: 251098 AF XY: 0.0416

Gnomad AFR exome AF: 0.0830

Gnomad AMR exome AF: 0.0672

Gnomad ASJ exome AF: 0.0152

Gnomad EAS exome AF: 0.000979

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0296

Gnomad OTH exome AF: 0.0389

GnomAD4 exome AF: 0.0335 AC: 48892 AN: 1461586 Hom.: 1035 Cov.: 31 AF XY: 0.0336 AC XY: 24466 AN XY: 727090

African (AFR) AF: 0.0806 AC: 2696 AN: 33464

American (AMR) AF: 0.0656 AC: 2933 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 437 AN: 26124

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.0462 AC: 3985 AN: 86228

European-Finnish (FIN) AF: 0.0937 AC: 5005 AN: 53400

Middle Eastern (MID) AF: 0.0370 AC: 213 AN: 5762

European-Non Finnish (NFE) AF: 0.0284 AC: 31606 AN: 1111824

Other (OTH) AF: 0.0331 AC: 1997 AN: 60384

GnomAD4 genome AF: 0.0530 AC: 8063 AN: 152200 Hom.: 276 Cov.: 32 AF XY: 0.0565 AC XY: 4200 AN XY: 74402

African (AFR) AF: 0.0815 AC: 3384 AN: 41524

American (AMR) AF: 0.0712 AC: 1088 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0458 AC: 221 AN: 4824

European-Finnish (FIN) AF: 0.101 AC: 1069 AN: 10588

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0310 AC: 2108 AN: 68018

Other (OTH) AF: 0.0464 AC: 98 AN: 2110

Alfa AF: 0.0344 Hom.: 435

Bravo AF: 0.0494

TwinsUK AF: 0.0267 AC: 99

ALSPAC AF: 0.0291 AC: 112

ESP6500AA AF: 0.0795 AC: 350

ESP6500EA AF: 0.0317 AC: 272

ExAC AF: 0.0418 AC: 5069

Asia WGS AF: 0.0270 AC: 94 AN: 3478

EpiCase AF: 0.0274

EpiControl AF: 0.0228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.4
DANN	Benign	0.71
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.24	N
PhyloP100		0.64
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.029	B
Vest4		0.023
MPC		0.092
ClinPred		0.00071	T
GERP RS		-0.44
Varity_R		0.055
gMVP		0.14
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17116138; hg19: chr11-113803666; COSMIC: COSV52743875;