rs897687

Positions:

• chr11-113985089-G-A
• chr11-113985089-G-C
• chr11-113985089-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.545-926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 152,212 control chromosomes in the GnomAD database, including 63,993 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 0.91 (63993 hom., cov: 33)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3A	NM_000869.6	c.545-926G>A		intron_variant		ENST00000504030.7	NP_000860.3
HTR3A	NM_001161772.3	c.500-926G>A		intron_variant			NP_001155244.1
HTR3A	NM_213621.4	c.545-926G>A		intron_variant			NP_998786.3
HTR3A	NR_046363.2	n.763-1429G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7	c.545-926G>A		intron_variant		1	NM_000869.6	ENSP00000424189	P1

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137746 AN: 152094 Hom.: 63966 Cov.: 33

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.931

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

GnomAD4 genome AF: 0.905 AC: 137821 AN: 152212 Hom.: 63993 Cov.: 33 AF XY: 0.909 AC XY: 67653 AN XY: 74434

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.931

Alfa AF: 0.945 Hom.: 8096

Bravo AF: 0.892

Asia WGS AF: 0.980 AC: 3407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.4
DANN	Benign	0.74

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: rs897687; hg19: chr11-113855811;