dbSNP rs3125: HTR2A:c.*121G>C (chr13-46834716-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000621.5(HTR2A):c.*121G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 707,280 control chromosomes in the GnomAD database, including 7,147 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 0.13 ( 1382 hom., cov: 32)

Exomes 𝑓: 0.14 ( 5765 hom. )

Consequence

HTR2A
NM_000621.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117

Publications

25 publications found

Variant links:

Genes affected

HTR2A (HGNC:5293): (5-hydroxytryptamine receptor 2A) This gene encodes one of the receptors for serotonin, a neurotransmitter with many roles. Mutations in this gene are associated with susceptibility to schizophrenia and obsessive-compulsive disorder, and are also associated with response to the antidepressant citalopram in patients with major depressive disorder (MDD). MDD patients who also have a mutation in intron 2 of this gene show a significantly reduced response to citalopram as this antidepressant downregulates expression of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

HTR2A 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 (AMR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5 link	c.*121G>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000542664.4	NP_000612.1	P28223-1
HTR2A	NM_001378924.1 link	c.*121G>C	3_prime_UTR_variant	Exon 4 of 4		NP_001365853.1
HTR2A	NM_001165947.5 link	c.*121G>C	3_prime_UTR_variant	Exon 3 of 3		NP_001159419.2	P28223

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 link	c.*121G>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_000621.5	ENSP00000437737.1		P28223-1
HTR2A	ENST00000543956.5 link	c.*121G>C		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000441861.2		A0A7P0PKG8

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19271

AN:

152032

Hom.:

1383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0804

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.140

AC:

77898

AN:

555132

Hom.:

5765

Cov.:

AF XY:

0.139

AC XY:

40180

AN XY:

289604

show subpopulations

African (AFR)

AF:

0.0799

AC:

1154

AN:

14452

American (AMR)

AF:

0.214

AC:

4228

AN:

19730

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

1851

AN:

14432

East Asian (EAS)

AF:

0.213

AC:

6943

AN:

32624

South Asian (SAS)

AF:

0.120

AC:

5584

AN:

46700

European-Finnish (FIN)

AF:

0.106

AC:

3661

AN:

34638

Middle Eastern (MID)

AF:

0.120

AC:

403

AN:

3360

European-Non Finnish (NFE)

AF:

0.139

AC:

49890

AN:

359644

Other (OTH)

AF:

0.142

AC:

4184

AN:

29552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

3242

6485

9727

12970

16212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.127

AC:

19282

AN:

152148

Hom.:

1382

Cov.:

AF XY:

0.126

AC XY:

9404

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0802

AC:

3329

AN:

41514

American (AMR)

AF:

0.188

AC:

2868

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

425

AN:

3472

East Asian (EAS)

AF:

0.175

AC:

906

AN:

5178

South Asian (SAS)

AF:

0.119

AC:

574

AN:

4822

European-Finnish (FIN)

AF:

0.110

AC:

1159

AN:

10582

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9572

AN:

67992

Other (OTH)

AF:

0.143

AC:

301

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

849

1697

2546

3394

4243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<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:

0.0645

Hom.:

Bravo

AF:

0.134

Asia WGS

AF:

0.136

AC:

475

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

0.11

(source)

DANN

Benign

0.60

PhyloP100

0.12

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