rs1176713

Positions:

• chr11-113989703-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000869.6(HTR3A):​c.1377A>G​(p.Leu459Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,613,658 control chromosomes in the GnomAD database, including 43,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.26 (5271 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38575 hom.)
• Consequence: HTR3A NM_000869.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

Genes affected

HTR3A (HGNC:5297): (5-hydroxytryptamine receptor 3A) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A 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 appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

HTR3A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 11-113989703-A-G is Benign according to our data. Variant chr11-113989703-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=1.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3A	NM_000869.6	c.1377A>G	p.Leu459Leu	synonymous_variant	9/9	ENST00000504030.7	NP_000860.3
HTR3A	NM_213621.4	c.1473A>G	p.Leu491Leu	synonymous_variant	8/8		NP_998786.3
HTR3A	NM_001161772.3	c.1332A>G	p.Leu444Leu	synonymous_variant	9/9		NP_001155244.1
HTR3A	NR_046363.2	n.1434A>G		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7	c.1377A>G	p.Leu459Leu	synonymous_variant	9/9	1	NM_000869.6	ENSP00000424189.2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38746 AN: 151972 Hom.: 5254 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.254

GnomAD3 exomes AF: 0.264 AC: 66232 AN: 250986 Hom.: 9451 AF XY: 0.255 AC XY: 34620 AN XY: 135666

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.409

Gnomad ASJ exome AF: 0.261

Gnomad EAS exome AF: 0.296

Gnomad SAS exome AF: 0.245

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.238

GnomAD4 exome AF: 0.226 AC: 330158 AN: 1461566 Hom.: 38575 Cov.: 36 AF XY: 0.225 AC XY: 163816 AN XY: 727076

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.255 AC: 38804 AN: 152092 Hom.: 5271 Cov.: 32 AF XY: 0.258 AC XY: 19186 AN XY: 74350

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.256

Alfa AF: 0.228 Hom.: 3489

Bravo AF: 0.262

Asia WGS AF: 0.275 AC: 958 AN: 3478

EpiCase AF: 0.217

EpiControl AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.6
DANN	Benign	0.64

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: rs1176713; hg19: chr11-113860425; COSMIC: COSV55467970; COSMIC: COSV55467970;