11-113987164-G-A

Position:

• chr11-113987164-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000869.6(HTR3A):​c.1138+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,073,514 control chromosomes in the GnomAD database, including 19,216 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 0.17 (2563 hom., cov: 32)
  • Exomes 𝑓: 0.18 (16653 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3A	NM_000869.6	c.1138+118G>A		intron_variant		ENST00000504030.7
HTR3A	NM_001161772.3	c.1093+118G>A		intron_variant
HTR3A	NM_213621.4	c.1234+118G>A		intron_variant
HTR3A	NR_046363.2	n.1195+118G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3A	ENST00000504030.7	c.1138+118G>A		intron_variant		1	NM_000869.6	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26348 AN: 152052 Hom.: 2563 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.184 AC: 169787 AN: 921344 Hom.: 16653 AF XY: 0.183 AC XY: 86825 AN XY: 473612

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.173 AC: 26349 AN: 152170 Hom.: 2563 Cov.: 32 AF XY: 0.175 AC XY: 13013 AN XY: 74396

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.174

Alfa AF: 0.179 Hom.: 331

Bravo AF: 0.163

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.21
DANN	Benign	0.68

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: rs1150220; hg19: chr11-113857886;