rs2276302

Variant names:

• chr11-113979418-G-A
• rs2276302
• NM_000869.6:c.264+141G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000869.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	NM_000869.6	MANE Select	c.264+141G>A		intron	N/A	NP_000860.3	P46098-1
	HTR3A	NM_213621.4		c.264+141G>A		intron	N/A	NP_998786.3	P46098-2
	HTR3A	NM_001161772.3		c.219+141G>A		intron	N/A	NP_001155244.1	P46098-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	ENST00000504030.7	TSL:1 MANE Select	c.264+141G>A		intron	N/A	ENSP00000424189.2	P46098-1
	HTR3A	ENST00000375498.6	TSL:1	c.282+141G>A		intron	N/A	ENSP00000364648.2	P46098-4
	HTR3A	ENST00000355556.6	TSL:2	c.282+141G>A		intron	N/A	ENSP00000347754.2	P46098-5

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

African (AFR) AF: 0.480 AC: 7305 AN: 15228

American (AMR) AF: 0.778 AC: 24691 AN: 31750

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 13137 AN: 18460

East Asian (EAS) AF: 0.871 AC: 28537 AN: 32756

South Asian (SAS) AF: 0.794 AC: 49479 AN: 62332

European-Finnish (FIN) AF: 0.628 AC: 21837 AN: 34790

Middle Eastern (MID) AF: 0.747 AC: 2160 AN: 2890

European-Non Finnish (NFE) AF: 0.691 AC: 221268 AN: 319988

Other (OTH) AF: 0.696 AC: 20847 AN: 29970

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

African (AFR) AF: 0.488 AC: 20140 AN: 41290

American (AMR) AF: 0.736 AC: 11221 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2474 AN: 3470

East Asian (EAS) AF: 0.856 AC: 4391 AN: 5128

South Asian (SAS) AF: 0.804 AC: 3859 AN: 4800

European-Finnish (FIN) AF: 0.615 AC: 6481 AN: 10530

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46660 AN: 67870

Other (OTH) AF: 0.667 AC: 1400 AN: 2098

Alfa AF: 0.678 Hom.: 112576

Bravo AF: 0.644

Asia WGS AF: 0.825 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.54
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2276302; hg19: chr11-113850140;