rs11607240

Positions:

• chr11-113981131-C-T

Variant summary

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

The NM_000869.6(HTR3A):​c.265-72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 925,392 control chromosomes in the GnomAD database, including 2,833 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 0.058 (380 hom., cov: 32)
  • Exomes 𝑓: 0.073 (2453 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3A	NM_000869.6	c.265-72C>T		intron_variant		ENST00000504030.7
HTR3A	NM_001161772.3	c.220-72C>T		intron_variant
HTR3A	NM_213621.4	c.265-72C>T		intron_variant
HTR3A	NR_046363.2	n.483-72C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3A	ENST00000504030.7	c.265-72C>T		intron_variant		1	NM_000869.6	P1

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8780 AN: 152208 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0734 AC: 56739 AN: 773066 Hom.: 2453 Cov.: 10 AF XY: 0.0727 AC XY: 29832 AN XY: 410092

Gnomad4 AFR exome AF: 0.0134

Gnomad4 AMR exome AF: 0.0695

Gnomad4 ASJ exome AF: 0.0308

Gnomad4 EAS exome AF: 0.000663

Gnomad4 SAS exome AF: 0.0724

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.0784

Gnomad4 OTH exome AF: 0.0659

GnomAD4 genome AF: 0.0576 AC: 8778 AN: 152326 Hom.: 380 Cov.: 32 AF XY: 0.0593 AC XY: 4418 AN XY: 74488

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0490

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0640

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0677 Hom.: 399

Bravo AF: 0.0487

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.4
DANN	Benign	0.81

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: rs11607240; hg19: chr11-113851853;