rs3737457

Positions:

• chr11-113982977-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.375-143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 912,376 control chromosomes in the GnomAD database, including 3,030 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 0.071 (823 hom., cov: 33)
  • Exomes 𝑓: 0.039 (2207 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3A	NM_000869.6	c.375-143G>A		intron_variant		ENST00000504030.7	NP_000860.3
HTR3A	NM_213621.4	c.375-143G>A		intron_variant			NP_998786.3
HTR3A	NM_001161772.3	c.330-143G>A		intron_variant			NP_001155244.1
HTR3A	NR_046363.2	n.593-143G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7	c.375-143G>A		intron_variant		1	NM_000869.6	ENSP00000424189.2

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10803 AN: 152062 Hom.: 808 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.00990

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0683

GnomAD4 exome AF: 0.0395 AC: 29996 AN: 760196 Hom.: 2207 AF XY: 0.0400 AC XY: 15914 AN XY: 397730

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.0977

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.0436

GnomAD4 genome AF: 0.0714 AC: 10872 AN: 152180 Hom.: 823 Cov.: 33 AF XY: 0.0724 AC XY: 5385 AN XY: 74404

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.00990

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0330 Hom.: 102

Bravo AF: 0.0862

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.52

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: rs3737457; hg19: chr11-113853699;