11-113931879-A-G

Position:

• chr11-113931879-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006028.5(HTR3B):​c.368+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,434,708 control chromosomes in the GnomAD database, including 301,013 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 0.71 (39529 hom., cov: 31)
  • Exomes 𝑓: 0.63 (261484 hom.)
• Consequence: HTR3B NM_006028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3B	NM_006028.5	c.368+12A>G		intron_variant		ENST00000260191.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3B	ENST00000260191.8	c.368+12A>G		intron_variant		1	NM_006028.5	P2
HTR3B	ENST00000537778.5	c.335+12A>G		intron_variant		1		A2
HTR3B	ENST00000543092.1	c.154+12A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108208 AN: 151870 Hom.: 39469 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.729

GnomAD3 exomes AF: 0.677 AC: 170084 AN: 251238 Hom.: 58421 AF XY: 0.671 AC XY: 91083 AN XY: 135790

Gnomad AFR exome AF: 0.873

Gnomad AMR exome AF: 0.769

Gnomad ASJ exome AF: 0.673

Gnomad EAS exome AF: 0.687

Gnomad SAS exome AF: 0.710

Gnomad FIN exome AF: 0.615

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.661

GnomAD4 exome AF: 0.634 AC: 813714 AN: 1282720 Hom.: 261484 Cov.: 19 AF XY: 0.636 AC XY: 411800 AN XY: 647466

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.761

Gnomad4 ASJ exome AF: 0.677

Gnomad4 EAS exome AF: 0.724

Gnomad4 SAS exome AF: 0.709

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.658

GnomAD4 genome AF: 0.713 AC: 108325 AN: 151988 Hom.: 39529 Cov.: 31 AF XY: 0.714 AC XY: 53045 AN XY: 74270

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.732

Alfa AF: 0.631 Hom.: 19424

Bravo AF: 0.726

Asia WGS AF: 0.719 AC: 2499 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	15
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.45		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1176746; hg19: chr11-113802601;