11-113931879-A-G

Variant names:

• chr11-113931879-A-G
• rs1176746
• NM_006028.5:c.368+12A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006028.5(HTR3B):​c.368+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,434,708 control chromosomes in the GnomAD database, including 301,013 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 0.71 (39529 hom., cov: 31)
  • Exomes 𝑓: 0.63 (261484 hom.)
• Consequence: HTR3B NM_006028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 18 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.368+12A>G		intron_variant	Intron 4 of 8	ENST00000260191.8	NP_006019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3B	ENST00000260191.8	c.368+12A>G		intron_variant	Intron 4 of 8	1	NM_006028.5	ENSP00000260191.2
HTR3B	ENST00000537778.5	c.335+12A>G		intron_variant	Intron 3 of 7	1		ENSP00000443118.1
HTR3B	ENST00000543092.1	c.152+12A>G		intron_variant	Intron 2 of 4	3		ENSP00000440894.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108208 AN: 151870 Hom.: 39469 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.729

GnomAD2 exomes AF: 0.677 AC: 170084 AN: 251238 AF XY: 0.671

Gnomad AFR exome AF: 0.873

Gnomad AMR exome AF: 0.769

Gnomad ASJ exome AF: 0.673

Gnomad EAS exome AF: 0.687

Gnomad FIN exome AF: 0.615

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.661

GnomAD4 exome AF: 0.634 AC: 813714 AN: 1282720 Hom.: 261484 Cov.: 19 AF XY: 0.636 AC XY: 411800 AN XY: 647466

African (AFR) AF: 0.875 AC: 26291 AN: 30030

American (AMR) AF: 0.761 AC: 33885 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 16877 AN: 24938

East Asian (EAS) AF: 0.724 AC: 28183 AN: 38924

South Asian (SAS) AF: 0.709 AC: 58576 AN: 82560

European-Finnish (FIN) AF: 0.608 AC: 32384 AN: 53292

Middle Eastern (MID) AF: 0.735 AC: 4018 AN: 5464

European-Non Finnish (NFE) AF: 0.609 AC: 577571 AN: 948436

Other (OTH) AF: 0.658 AC: 35929 AN: 54576

GnomAD4 genome AF: 0.713 AC: 108325 AN: 151988 Hom.: 39529 Cov.: 31 AF XY: 0.714 AC XY: 53045 AN XY: 74270

African (AFR) AF: 0.869 AC: 36034 AN: 41476

American (AMR) AF: 0.749 AC: 11422 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2364 AN: 3462

East Asian (EAS) AF: 0.700 AC: 3613 AN: 5158

South Asian (SAS) AF: 0.716 AC: 3452 AN: 4822

European-Finnish (FIN) AF: 0.616 AC: 6500 AN: 10548

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42580 AN: 67960

Other (OTH) AF: 0.732 AC: 1545 AN: 2112

Alfa AF: 0.656 Hom.: 26423

Bravo AF: 0.726

Asia WGS AF: 0.719 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	15
DANN	Benign	0.38
PhyloP100		-0.30
PromoterAI		0.0044	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.45		Position offset: 0

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

Other links and lift over

dbSNP: rs1176746; hg19: chr11-113802601; COSMIC: COSV107278876;