11-113918658-A-T

Variant names:

• chr11-113918658-A-T
• rs4938058
• NM_006028.5:c.213+9203A>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.213+9203A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000708 in 141,334 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: 𝑓 0.0000071 (0 hom., cov: 26)
• Consequence: HTR3B NM_006028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 10 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=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.213+9203A>T		intron_variant	Intron 2 of 8	ENST00000260191.8	NP_006019.1
HTR3B	NM_001363563.2	c.180+9203A>T		intron_variant	Intron 1 of 7		NP_001350492.1
HTR3B	XM_024448767.2	c.-82+9203A>T		intron_variant	Intron 2 of 8		XP_024304535.1
HTR3B	XM_047427869.1	c.180+9203A>T		intron_variant	Intron 1 of 5		XP_047283825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3B	ENST00000260191.8	c.213+9203A>T		intron_variant	Intron 2 of 8	1	NM_006028.5	ENSP00000260191.2
HTR3B	ENST00000537778.5	c.180+9203A>T		intron_variant	Intron 1 of 7	1		ENSP00000443118.1

Frequencies

GnomAD3 genomes AF: 0.00000708 AC: 1 AN: 141272 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000708 AC: 1 AN: 141334 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 68164

African (AFR) AF: 0.00 AC: 0 AN: 37616

American (AMR) AF: 0.00 AC: 0 AN: 13872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 4834

South Asian (SAS) AF: 0.00 AC: 0 AN: 4478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65692

Other (OTH) AF: 0.00 AC: 0 AN: 1968

Alfa AF: 0.00 Hom.: 63

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.56
PhyloP100		-0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4938058; hg19: chr11-113789380;