rs1176744

Variant names:

• chr11-113932306-A-C
• rs1176744
• NM_006028.5:c.386A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-113932306-A-C
• chr11-113932306-A-G
• chr11-113932306-A-T

Variant summary

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

The NM_006028.5(HTR3B):​c.386A>C​(p.Tyr129Ser) variant causes a missense change. The variant allele was found at a frequency of 0.326 in 1,609,780 control chromosomes in the GnomAD database, including 87,633 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.36 (9954 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77679 hom.)
• Consequence: HTR3B NM_006028.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02
• Publications: 119 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=0.0025437474).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.386A>C	p.Tyr129Ser	missense_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.386A>C	p.Tyr129Ser	missense_variant	Exon 5 of 9	1	NM_006028.5	ENSP00000260191.2
HTR3B	ENST00000537778.5	c.353A>C	p.Tyr118Ser	missense_variant	Exon 4 of 8	1		ENSP00000443118.1
HTR3B	ENST00000543092.1	c.170A>C	p.Tyr57Ser	missense_variant	Exon 3 of 5	3		ENSP00000440894.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54166 AN: 151850 Hom.: 9929 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.355

GnomAD2 exomes AF: 0.333 AC: 83424 AN: 250544 AF XY: 0.335

Gnomad AFR exome AF: 0.436

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.161

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.323 AC: 471301 AN: 1457812 Hom.: 77679 Cov.: 32 AF XY: 0.326 AC XY: 236649 AN XY: 725386

African (AFR) AF: 0.440 AC: 14682 AN: 33364

American (AMR) AF: 0.359 AC: 15993 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8825 AN: 26082

East Asian (EAS) AF: 0.226 AC: 8957 AN: 39686

South Asian (SAS) AF: 0.418 AC: 35926 AN: 86010

European-Finnish (FIN) AF: 0.303 AC: 16200 AN: 53396

Middle Eastern (MID) AF: 0.343 AC: 1972 AN: 5752

European-Non Finnish (NFE) AF: 0.315 AC: 348919 AN: 1108714

Other (OTH) AF: 0.329 AC: 19827 AN: 60254

GnomAD4 genome AF: 0.357 AC: 54235 AN: 151968 Hom.: 9954 Cov.: 32 AF XY: 0.357 AC XY: 26521 AN XY: 74280

African (AFR) AF: 0.436 AC: 18077 AN: 41442

American (AMR) AF: 0.373 AC: 5693 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3466

East Asian (EAS) AF: 0.172 AC: 888 AN: 5160

South Asian (SAS) AF: 0.417 AC: 2012 AN: 4820

European-Finnish (FIN) AF: 0.309 AC: 3267 AN: 10560

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21977 AN: 67950

Other (OTH) AF: 0.354 AC: 745 AN: 2106

Alfa AF: 0.331 Hom.: 36164

Bravo AF: 0.360

TwinsUK AF: 0.321 AC: 1190

ALSPAC AF: 0.310 AC: 1194

ESP6500AA AF: 0.428 AC: 1883

ESP6500EA AF: 0.324 AC: 2783

ExAC AF: 0.337 AC: 40852

Asia WGS AF: 0.311 AC: 1084 AN: 3478

EpiCase AF: 0.326

EpiControl AF: 0.321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.26
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.089	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-3.2	N;.
PhyloP100		5.0
PrimateAI	Benign	0.35	T
PROVEAN	Benign	4.3	N;N
REVEL	Benign	0.25
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.051
ClinPred		0.0049	T
GERP RS		4.6
Varity_R		0.080
gMVP		0.51
Mutation Taster		=97/3	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: rs1176744; hg19: chr11-113803028; COSMIC: COSV52743661;