dbSNP rs6316: HTR2A:c.-328-854A>G (chr13-46897088-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001378924.1(HTR2A):c.-328-854A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 440,608 control chromosomes in the GnomAD database, including 220 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 0.027 ( 189 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 31 hom. )

Consequence

HTR2A
NM_001378924.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.48

Publications

5 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:

ENSG00000301465 (HGNC:):

ENSG00000301465 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=-0.54).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378924.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HTR2A	NM_001378924.1		c.-328-854A>G	intron	N/A	NP_001365853.1	P28223-1
HTR2A	NM_000621.5	MANE Select	c.-743A>G	upstream_gene	N/A	NP_000612.1	P28223-1
HTR2A	NM_001165947.5		c.-492A>G	upstream_gene	N/A	NP_001159419.2	A0A7P0PKG8

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
ENSG00000301465	ENST00000778998.1	n.118T>C	non_coding_transcript_exon	Exon 1 of 2
ENSG00000301465	ENST00000779000.1	n.63T>C	non_coding_transcript_exon	Exon 1 of 2
ENSG00000301465	ENST00000778995.1	n.111+4545T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0275

AC:

4180

AN:

152140

Hom.:

189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0177

GnomAD4 exome

AF:

0.00323

AC:

932

AN:

288350

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

423

AN XY:

150414

show subpopulations

African (AFR)

AF:

0.0984

AC:

712

AN:

7236

American (AMR)

AF:

0.00705

AC:

AN:

7516

Ashkenazi Jewish (ASJ)

AF:

0.000104

AC:

AN:

9640

East Asian (EAS)

AF:

0.00

AC:

AN:

16500

South Asian (SAS)

AF:

0.000185

AC:

AN:

27022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18820

Middle Eastern (MID)

AF:

0.00357

AC:

AN:

1400

European-Non Finnish (NFE)

AF:

0.000126

AC:

AN:

182486

Other (OTH)

AF:

0.00750

AC:

133

AN:

17730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

131

174

218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0275

AC:

4185

AN:

152258

Hom.:

189

Cov.:

AF XY:

0.0268

AC XY:

1996

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0965

AC:

4007

AN:

41508

American (AMR)

AF:

0.00817

AC:

125

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000414

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68020

Other (OTH)

AF:

0.0175

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

200

401

601

802

1002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0341

Hom.:

Bravo

AF:

0.0311

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

2.5

PromoterAI

0.14

Neutral

(source)

Splicing

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