rs2276307

chr11-113933165-A-G

Variant summary

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

The NM_006028.5(HTR3B):c.696+72A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,460,512 control chromosomes in the GnomAD database, including 38,659 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 0.20 (3250 hom., cov: 32)
  • Exomes 𝑓: 0.23 (35409 hom.)
• Consequence: HTR3B NM_006028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3B	NM_006028.5	c.696+72A>G		intron_variant		ENST00000260191.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3B	ENST00000260191.8	c.696+72A>G		intron_variant		1	NM_006028.5	P2
HTR3B	ENST00000537778.5	c.663+72A>G		intron_variant		1		A2
HTR3B	ENST00000543092.1	c.482+72A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30123 AN: 152000 Hom.: 3240 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.230 AC: 301235 AN: 1308394 Hom.: 35409 AF XY: 0.234 AC XY: 151564 AN XY: 648982

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.198 AC: 30139 AN: 152118 Hom.: 3250 Cov.: 32 AF XY: 0.198 AC XY: 14689 AN XY: 74364

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.202

Alfa AF: 0.224 Hom.: 2201

Bravo AF: 0.194

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.37
Dann	Benign	0.34

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: rs2276307; hg19: chr11-113803887; COSMIC: COSV52747587;