Genetic Variant NM_006028.5:c.*427G>A (chr11-113946564-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006028.5(HTR3B):c.*427G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 155,416 control chromosomes in the GnomAD database, including 2,118 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 0.16 ( 2107 hom., cov: 31)

Exomes 𝑓: 0.039 ( 11 hom. )

Consequence

HTR3B
NM_006028.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.631

Publications

14 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

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.*427G>A		3_prime_UTR	Exon 9 of 9	NP_006019.1	O95264-1
	HTR3B	NM_001363563.2		c.*427G>A		3_prime_UTR	Exon 8 of 8	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.*427G>A		3_prime_UTR	Exon 9 of 9	ENSP00000260191.2	O95264-1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24900

AN:

151828

Hom.:

2107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.177

GnomAD4 exome

AF:

0.0386

AC:

134

AN:

3470

Hom.:

Cov.:

AF XY:

0.0468

AC XY:

AN XY:

2074

show subpopulations

African (AFR)

AF:

0.0500

AC:

AN:

American (AMR)

AF:

0.00741

AC:

AN:

540

Ashkenazi Jewish (ASJ)

AF:

0.0250

AC:

AN:

East Asian (EAS)

AF:

0.0317

AC:

AN:

126

South Asian (SAS)

AF:

0.0133

AC:

AN:

526

European-Finnish (FIN)

AF:

0.0294

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0547

AC:

113

AN:

2066

Other (OTH)

AF:

0.0259

AC:

AN:

116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.164

AC:

24902

AN:

151946

Hom.:

2107

Cov.:

AF XY:

0.164

AC XY:

12144

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.157

AC:

6519

AN:

41418

American (AMR)

AF:

0.135

AC:

2063

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

808

AN:

3470

East Asian (EAS)

AF:

0.108

AC:

558

AN:

5158

South Asian (SAS)

AF:

0.141

AC:

683

AN:

4830

European-Finnish (FIN)

AF:

0.164

AC:

1726

AN:

10556

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11957

AN:

67922

Other (OTH)

AF:

0.176

AC:

371

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1038

2076

3113

4151

5189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.170

Hom.:

3668

Bravo

AF:

0.159

Asia WGS

AF:

0.108

AC:

373

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.3

(source)

DANN

Benign

0.53

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over