rs11604247

Variant names:

• chr11-113976182-C-T
• rs11604247
• NM_000869.6:c.67+790C>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.67+790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,140 control chromosomes in the GnomAD database, including 1,529 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 0.13 (1529 hom., cov: 31)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3A	NM_000869.6	c.67+790C>T		intron_variant	Intron 1 of 8	ENST00000504030.7	NP_000860.3
HTR3A	NM_213621.4	c.67+790C>T		intron_variant	Intron 1 of 7		NP_998786.3
HTR3A	NR_046363.2	n.285+790C>T		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7	c.67+790C>T		intron_variant	Intron 1 of 8	1	NM_000869.6	ENSP00000424189.2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19483 AN: 152022 Hom.: 1512 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.128 AC: 19546 AN: 152140 Hom.: 1529 Cov.: 31 AF XY: 0.131 AC XY: 9760 AN XY: 74376

African (AFR) AF: 0.153 AC: 6367 AN: 41514

American (AMR) AF: 0.203 AC: 3097 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3470

East Asian (EAS) AF: 0.187 AC: 964 AN: 5162

South Asian (SAS) AF: 0.182 AC: 877 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1528 AN: 10586

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0919 AC: 6248 AN: 67990

Other (OTH) AF: 0.122 AC: 257 AN: 2110

Alfa AF: 0.102 Hom.: 3690

Bravo AF: 0.134

Asia WGS AF: 0.212 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.87
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11604247; hg19: chr11-113846904;