11-113985089-G-A

Variant names:

• chr11-113985089-G-A
• rs897687
• NM_000869.6:c.545-926G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	NM_000869.6	MANE Select	c.545-926G>A		intron	N/A	NP_000860.3
	HTR3A	NM_213621.4		c.545-926G>A		intron	N/A	NP_998786.3
	HTR3A	NM_001161772.3		c.500-926G>A		intron	N/A	NP_001155244.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	ENST00000504030.7	TSL:1 MANE Select	c.545-926G>A		intron	N/A	ENSP00000424189.2
	HTR3A	ENST00000375498.6	TSL:1	c.563-926G>A		intron	N/A	ENSP00000364648.2
	HTR3A	ENST00000355556.6	TSL:2	c.563-926G>A		intron	N/A	ENSP00000347754.2

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

African (AFR) AF: 0.673 AC: 27906 AN: 41456

American (AMR) AF: 0.964 AC: 14746 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3464 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.998 AC: 4820 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10614 AN: 10614

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67922 AN: 68042

Other (OTH) AF: 0.931 AC: 1971 AN: 2116

Alfa AF: 0.933 Hom.: 8269

Bravo AF: 0.892

Asia WGS AF: 0.980 AC: 3407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.4
DANN	Benign	0.74
PhyloP100		0.028
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs897687; hg19: chr11-113855811;