Genetic Variant HTR3A:c.1138+118G>A (chr11-113987164-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_000869.6(HTR3A):c.1138+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,073,514 control chromosomes in the GnomAD database, including 19,216 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 0.17 ( 2563 hom., cov: 32)

Exomes 𝑓: 0.18 ( 16653 hom. )

Consequence

HTR3A
NM_000869.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.475

Publications

9 publications found

Variant links:

Genes affected

HTR3A (HGNC:5297): (5-hydroxytryptamine receptor 3A) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A 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 appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

HTR3A links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HTR3A	NM_000869.6 link	c.1138+118G>A	intron_variant	Intron 8 of 8	ENST00000504030.7	NP_000860.3	P46098-1B4E398
HTR3A	NM_213621.4 link	c.1234+118G>A	intron_variant	Intron 7 of 7		NP_998786.3	P46098-2B4E398
HTR3A	NM_001161772.3 link	c.1093+118G>A	intron_variant	Intron 8 of 8		NP_001155244.1	P46098-3
HTR3A	NR_046363.2 link	n.1195+118G>A	intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7 link	c.1138+118G>A		intron_variant	Intron 8 of 8	1	NM_000869.6	ENSP00000424189.2		P46098-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26348

AN:

152052

Hom.:

2563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.176

GnomAD4 exome

AF:

0.184

AC:

169787

AN:

921344

Hom.:

16653

AF XY:

0.183

AC XY:

86825

AN XY:

473612

show subpopulations

African (AFR)

AF:

0.108

AC:

2457

AN:

22846

American (AMR)

AF:

0.136

AC:

4894

AN:

36100

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

5486

AN:

22316

East Asian (EAS)

AF:

0.124

AC:

4227

AN:

34142

South Asian (SAS)

AF:

0.143

AC:

10200

AN:

71238

European-Finnish (FIN)

AF:

0.238

AC:

8356

AN:

35058

Middle Eastern (MID)

AF:

0.172

AC:

767

AN:

4468

European-Non Finnish (NFE)

AF:

0.192

AC:

125371

AN:

652362

Other (OTH)

AF:

0.188

AC:

8029

AN:

42814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

7364

14729

22093

29458

36822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3172

6344

9516

12688

15860

<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:

0.173

AC:

26349

AN:

152170

Hom.:

2563

Cov.:

AF XY:

0.175

AC XY:

13013

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.115

AC:

4774

AN:

41528

American (AMR)

AF:

0.149

AC:

2281

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3470

East Asian (EAS)

AF:

0.144

AC:

743

AN:

5168

South Asian (SAS)

AF:

0.135

AC:

654

AN:

4830

European-Finnish (FIN)

AF:

0.234

AC:

2473

AN:

10586

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

13986

AN:

67974

Other (OTH)

AF:

0.174

AC:

368

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1086

2172

3257

4343

5429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.176

Hom.:

337

Bravo

AF:

0.163

Asia WGS

AF:

0.125

AC:

436

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.21

(source)

DANN

Benign

0.68

PhyloP100

-0.47

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over