11-113942891-T-A

Position:

• chr11-113942891-T-A

Variant summary

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

The NM_006028.5(HTR3B):​c.697-91T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 1,030,146 control chromosomes in the GnomAD database, including 2,048 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 0.086 (917 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1131 hom.)
• Consequence: HTR3B NM_006028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.697-91T>A		intron_variant		ENST00000260191.8	NP_006019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3B	ENST00000260191.8	c.697-91T>A		intron_variant		1	NM_006028.5	ENSP00000260191	P2
HTR3B	ENST00000537778.5	c.664-91T>A		intron_variant		1		ENSP00000443118	A2
HTR3B	ENST00000543092.1	c.483-1682T>A		intron_variant		3		ENSP00000440894

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13046 AN: 152022 Hom.: 910 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0467

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0314

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.0390 AC: 34211 AN: 878006 Hom.: 1131 AF XY: 0.0385 AC XY: 17395 AN XY: 451446

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.0723

Gnomad4 ASJ exome AF: 0.0167

Gnomad4 EAS exome AF: 0.000460

Gnomad4 SAS exome AF: 0.0460

Gnomad4 FIN exome AF: 0.0941

Gnomad4 NFE exome AF: 0.0283

Gnomad4 OTH exome AF: 0.0438

GnomAD4 genome AF: 0.0860 AC: 13080 AN: 152140 Hom.: 917 Cov.: 32 AF XY: 0.0893 AC XY: 6644 AN XY: 74368

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0870

Gnomad4 ASJ AF: 0.0181

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0461

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0314

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0264 Hom.: 27

Bravo AF: 0.0873

Asia WGS AF: 0.0340 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.39

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: rs1176761; hg19: chr11-113813613;