11-113933165-A-T

Variant names:

• chr11-113933165-A-T
• rs2276307
• NM_006028.5:c.696+72A>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.696+72A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,310,278 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: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: HTR3B NM_006028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• 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=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.696+72A>T		intron_variant	Intron 6 of 8	ENST00000260191.8	NP_006019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3B	ENST00000260191.8	c.696+72A>T		intron_variant	Intron 6 of 8	1	NM_006028.5	ENSP00000260191.2
HTR3B	ENST00000537778.5	c.663+72A>T		intron_variant	Intron 5 of 7	1		ENSP00000443118.1
HTR3B	ENST00000543092.1	c.480+72A>T		intron_variant	Intron 4 of 4	3		ENSP00000440894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000130 AC: 17 AN: 1310278 Hom.: 0 AF XY: 0.0000138 AC XY: 9 AN XY: 649932

African (AFR) AF: 0.00 AC: 0 AN: 29394

American (AMR) AF: 0.00 AC: 0 AN: 35528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22038

East Asian (EAS) AF: 0.00 AC: 0 AN: 38276

South Asian (SAS) AF: 0.00 AC: 0 AN: 73088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4220

European-Non Finnish (NFE) AF: 0.0000169 AC: 17 AN: 1003342

Other (OTH) AF: 0.00 AC: 0 AN: 54418

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.54
PhyloP100		-0.48

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: rs2276307; hg19: chr11-113803887;