11-113904553-T-C

Variant names:

• chr11-113904553-T-C
• rs3758987
• XM_024448767.2:c.-242-4742T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The XM_024448767.2(HTR3B):​c.-242-4742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 170,498 control chromosomes in the GnomAD database, including 8,346 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 0.32 (7694 hom., cov: 32)
  • Exomes 𝑓: 0.26 (652 hom.)
• Consequence: HTR3B XM_024448767.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000260191.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3B	NM_006028.5	MANE Select	c.-381T>C		upstream_gene	N/A	NP_006019.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3B	ENST00000260191.8	TSL:1 MANE Select	c.-381T>C		upstream_gene	N/A	ENSP00000260191.2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47986 AN: 151892 Hom.: 7681 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.257 AC: 4760 AN: 18488 Hom.: 652 AF XY: 0.257 AC XY: 2414 AN XY: 9384

African (AFR) AF: 0.341 AC: 210 AN: 616

American (AMR) AF: 0.286 AC: 269 AN: 940

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 159 AN: 658

East Asian (EAS) AF: 0.219 AC: 247 AN: 1128

South Asian (SAS) AF: 0.290 AC: 265 AN: 914

European-Finnish (FIN) AF: 0.277 AC: 221 AN: 798

Middle Eastern (MID) AF: 0.176 AC: 18 AN: 102

European-Non Finnish (NFE) AF: 0.250 AC: 2983 AN: 11916

Other (OTH) AF: 0.274 AC: 388 AN: 1416

GnomAD4 genome AF: 0.316 AC: 48031 AN: 152010 Hom.: 7694 Cov.: 32 AF XY: 0.317 AC XY: 23577 AN XY: 74296

African (AFR) AF: 0.372 AC: 15409 AN: 41458

American (AMR) AF: 0.331 AC: 5046 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 931 AN: 3456

East Asian (EAS) AF: 0.175 AC: 904 AN: 5180

South Asian (SAS) AF: 0.375 AC: 1806 AN: 4820

European-Finnish (FIN) AF: 0.317 AC: 3349 AN: 10550

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19591 AN: 67974

Other (OTH) AF: 0.302 AC: 638 AN: 2116

Alfa AF: 0.295 Hom.: 17302

Bravo AF: 0.315

Asia WGS AF: 0.310 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.80
PhyloP100		1.7
PromoterAI		0.017	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3758987; hg19: chr11-113775275;