Variant 11-113932286-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006028.5(HTR3B):c.369-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,607,934 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 96 hom. )

Consequence

HTR3B
NM_006028.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001801

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0480

Variant links:

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]

HTR3B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 11-113932286-T-C is Benign according to our data. Variant chr11-113932286-T-C is described in ClinVar as [Benign]. Clinvar id is 790848.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00192 (292/152322) while in subpopulation SAS AF= 0.0315 (152/4826). AF 95% confidence interval is 0.0274. There are 4 homozygotes in gnomad4. There are 203 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3B	NM_006028.5 linkuse as main transcript	c.369-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000260191.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
HTR3B	ENST00000260191.8 linkuse as main transcript	c.369-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_006028.5	P2	O95264-1
HTR3B	ENST00000537778.5 linkuse as main transcript	c.336-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		A2	O95264-2
HTR3B	ENST00000543092.1 linkuse as main transcript	c.155-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

293

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0255

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00576

AC:

1433

AN:

248608

Hom.:

AF XY:

0.00670

AC XY:

900

AN XY:

134292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000592

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0279

Gnomad SAS exome

AF:

0.0300

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00260

AC:

3791

AN:

1455612

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

2379

AN XY:

724350

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.0000455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0334

Gnomad4 SAS exome

AF:

0.0263

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000181

Gnomad4 OTH exome

AF:

0.00304

GnomAD4 genome

AF:

0.00192

AC:

292

AN:

152322

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0255

Gnomad4 SAS

AF:

0.0315

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.00138

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.24

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.070

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over