dbSNP rs3737457: HTR3A:c.375-143G>A (chr11-113982977-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.375-143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 912,376 control chromosomes in the GnomAD database, including 3,030 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 0.071 ( 823 hom., cov: 33)

Exomes 𝑓: 0.039 ( 2207 hom. )

Consequence

HTR3A
NM_000869.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.893

Publications

7 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:

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=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
HTR3A	NM_000869.6 link	c.375-143G>A	intron_variant	Intron 4 of 8	ENST00000504030.7	NP_000860.3
HTR3A	NM_213621.4 link	c.375-143G>A	intron_variant	Intron 4 of 7		NP_998786.3
HTR3A	NM_001161772.3 link	c.330-143G>A	intron_variant	Intron 4 of 8		NP_001155244.1
HTR3A	NR_046363.2 link	n.593-143G>A	intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7 link	c.375-143G>A		intron_variant	Intron 4 of 8	1	NM_000869.6	ENSP00000424189.2

Frequencies

GnomAD3 genomes

AF:

0.0710

AC:

10803

AN:

152062

Hom.:

808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.00990

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0683

GnomAD4 exome

AF:

0.0395

AC:

29996

AN:

760196

Hom.:

2207

AF XY:

0.0400

AC XY:

15914

AN XY:

397730

show subpopulations

African (AFR)

AF:

0.153

AC:

2965

AN:

19436

American (AMR)

AF:

0.243

AC:

8509

AN:

34968

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

282

AN:

20048

East Asian (EAS)

AF:

0.113

AC:

3822

AN:

33694

South Asian (SAS)

AF:

0.0977

AC:

6380

AN:

65332

European-Finnish (FIN)

AF:

0.0105

AC:

411

AN:

39084

Middle Eastern (MID)

AF:

0.0338

AC:

130

AN:

3842

European-Non Finnish (NFE)

AF:

0.0116

AC:

5878

AN:

506644

Other (OTH)

AF:

0.0436

AC:

1619

AN:

37148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1405

2810

4215

5620

7025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.0714

AC:

10872

AN:

152180

Hom.:

823

Cov.:

AF XY:

0.0724

AC XY:

5385

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.149

AC:

6191

AN:

41516

American (AMR)

AF:

0.154

AC:

2345

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3470

East Asian (EAS)

AF:

0.123

AC:

636

AN:

5164

South Asian (SAS)

AF:

0.116

AC:

561

AN:

4818

European-Finnish (FIN)

AF:

0.00990

AC:

105

AN:

10608

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0122

AC:

827

AN:

68006

Other (OTH)

AF:

0.0733

AC:

155

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

477

955

1432

1910

2387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0331

Hom.:

115

Bravo

AF:

0.0862

Asia WGS

AF:

0.146

AC:

507

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.28

(source)

DANN

Benign

0.52

PhyloP100

-0.89

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