11-113942891-T-C

Variant names:

• chr11-113942891-T-C
• rs1176761
• NM_006028.5:c.697-91T>C

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.697-91T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 878,268 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: 0.0000023 (0 hom.)
• Consequence: HTR3B NM_006028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 5 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=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006028.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3B	NM_006028.5	MANE Select	c.697-91T>C		intron	N/A	NP_006019.1	O95264-1
	HTR3B	NM_001363563.2		c.664-91T>C		intron	N/A	NP_001350492.1	O95264-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3B	ENST00000260191.8	TSL:1 MANE Select	c.697-91T>C		intron	N/A	ENSP00000260191.2	O95264-1
	HTR3B	ENST00000537778.5	TSL:1	c.664-91T>C		intron	N/A	ENSP00000443118.1	O95264-2
	HTR3B	ENST00000543092.1	TSL:3	c.481-1682T>C		intron	N/A	ENSP00000440894.1	H0YFX8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000228 AC: 2 AN: 878268 Hom.: 0 AF XY: 0.00000221 AC XY: 1 AN XY: 451558

African (AFR) AF: 0.00 AC: 0 AN: 22078

American (AMR) AF: 0.00 AC: 0 AN: 36624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21432

East Asian (EAS) AF: 0.00 AC: 0 AN: 34808

South Asian (SAS) AF: 0.00 AC: 0 AN: 69680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4462

European-Non Finnish (NFE) AF: 0.00000167 AC: 1 AN: 598286

Other (OTH) AF: 0.0000246 AC: 1 AN: 40700

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.69
PhyloP100		-0.75

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1176761;

hg19: chr11-113813613;