11-113904832-A-T

Variant names:

• chr11-113904832-A-T
• rs35312182
• NM_006028.5:c.-102A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006028.5(HTR3B):​c.-102A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000172 in 579,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: HTR3B NM_006028.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.-102A>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000260191.8	NP_006019.1
HTR3B	XM_024448767.2	c.-242-4463A>T		intron_variant	Intron 1 of 8		XP_024304535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3B	ENST00000260191.8	c.-102A>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_006028.5	ENSP00000260191.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000172 AC: 1 AN: 579892 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 307764

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15460

American (AMR) AF: 0.00 AC: 0 AN: 35100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15742

East Asian (EAS) AF: 0.00 AC: 0 AN: 25864

South Asian (SAS) AF: 0.00 AC: 0 AN: 55698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2634

European-Non Finnish (NFE) AF: 0.00000276 AC: 1 AN: 361894

Other (OTH) AF: 0.00 AC: 0 AN: 28358

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.65
PhyloP100		0.64
PromoterAI		-0.045	Neutral

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

Other links and lift over

dbSNP: rs35312182; hg19: chr11-113775554;