rs2276302

Positions:

• chr11-113979418-G-A
• chr11-113979418-G-C
• chr11-113979418-G-T

Variant summary

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

The NM_000869.6(HTR3A):​c.264+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 699,800 control chromosomes in the GnomAD database, including 172,359 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 0.64 (32350 hom., cov: 29)
  • Exomes 𝑓: 0.71 (140009 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472

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 (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3A	NM_000869.6	c.264+141G>A		intron_variant		ENST00000504030.7	NP_000860.3
HTR3A	NM_001161772.3	c.219+141G>A		intron_variant			NP_001155244.1
HTR3A	NM_213621.4	c.264+141G>A		intron_variant			NP_998786.3
HTR3A	NR_046363.2	n.482+141G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7	c.264+141G>A		intron_variant		1	NM_000869.6	ENSP00000424189	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97389 AN: 151518 Hom.: 32319 Cov.: 29

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.663

GnomAD4 exome AF: 0.710 AC: 389261 AN: 548164 Hom.: 140009 AF XY: 0.716 AC XY: 212490 AN XY: 296820

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.778

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.794

Gnomad4 FIN exome AF: 0.628

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.696

GnomAD4 genome AF: 0.643 AC: 97468 AN: 151636 Hom.: 32350 Cov.: 29 AF XY: 0.644 AC XY: 47706 AN XY: 74068

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.667

Alfa AF: 0.687 Hom.: 47677

Bravo AF: 0.644

Asia WGS AF: 0.825 AC: 2870 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	7.5
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs2276302; hg19: chr11-113850140;