rs12288145

Positions:

• chr11-113943310-G-A

Variant summary

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

The NM_006028.5(HTR3B):​c.907+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 807,448 control chromosomes in the GnomAD database, including 709 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 0.033 (102 hom., cov: 32)
  • Exomes 𝑓: 0.040 (607 hom.)
• Consequence: HTR3B NM_006028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

Genes affected

HTR3B (HGNC:5298): (5-hydroxytryptamine receptor 3B) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit B 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 is not functional as a homomeric complex, but a pentaheteromeric complex with subunit A (HTR3A) displays the full functional features of this receptor. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3B	NM_006028.5	c.907+118G>A		intron_variant		ENST00000260191.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3B	ENST00000260191.8	c.907+118G>A		intron_variant		1	NM_006028.5	P2
HTR3B	ENST00000537778.5	c.874+118G>A		intron_variant		1		A2
HTR3B	ENST00000543092.1	c.483-1263G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4979 AN: 152070 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.0587

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.0395 AC: 25911 AN: 655260 Hom.: 607 AF XY: 0.0415 AC XY: 14240 AN XY: 343148

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.0257

Gnomad4 ASJ exome AF: 0.0737

Gnomad4 EAS exome AF: 0.000249

Gnomad4 SAS exome AF: 0.0644

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.0415

Gnomad4 OTH exome AF: 0.0433

GnomAD4 genome AF: 0.0327 AC: 4984 AN: 152188 Hom.: 102 Cov.: 32 AF XY: 0.0317 AC XY: 2359 AN XY: 74400

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.000776

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0317 Hom.: 9

Bravo AF: 0.0334

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.21

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: rs12288145; hg19: chr11-113814032;