11-113977078-A-T

Variant names:

• chr11-113977078-A-T
• rs1176724
• NM_000869.6:c.68-693A>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.68-693A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 151,988 control chromosomes in the GnomAD database, including 63,645 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 0.90 (63645 hom., cov: 29)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 5 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=-0.94).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	NM_000869.6	MANE Select	c.68-693A>T		intron	N/A	NP_000860.3	P46098-1
	HTR3A	NM_213621.4		c.68-693A>T		intron	N/A	NP_998786.3	P46098-2
	HTR3A	NR_046363.2		n.286-693A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	ENST00000504030.7	TSL:1 MANE Select	c.68-693A>T		intron	N/A	ENSP00000424189.2	P46098-1
	HTR3A	ENST00000375498.6	TSL:1	c.86-693A>T		intron	N/A	ENSP00000364648.2	P46098-4
	HTR3A	ENST00000355556.6	TSL:2	c.86-693A>T		intron	N/A	ENSP00000347754.2	P46098-5

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137192 AN: 151872 Hom.: 63619 Cov.: 29

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.933

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

GnomAD4 genome AF: 0.903 AC: 137268 AN: 151988 Hom.: 63645 Cov.: 29 AF XY: 0.907 AC XY: 67334 AN XY: 74268

African (AFR) AF: 0.665 AC: 27481 AN: 41354

American (AMR) AF: 0.963 AC: 14705 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3469 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5134 AN: 5134

South Asian (SAS) AF: 0.999 AC: 4795 AN: 4800

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67905 AN: 68022

Other (OTH) AF: 0.934 AC: 1974 AN: 2114

Alfa AF: 0.944 Hom.: 3455

Bravo AF: 0.889

Asia WGS AF: 0.979 AC: 3404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.49
PhyloP100		0.023
PromoterAI		0.0058	Neutral
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: rs1176724; hg19: chr11-113847800;