Genetic Variant ENSG00000301465:n.118T>C (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 ENST00000778998.1(ENSG00000301465):n.118T>C variant causes a non coding transcript exon 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

ENSG00000301465
ENST00000778998.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.48

Publications

5 publications found

Variant links:

Genes affected

ENSG00000301465 (HGNC:):

ENSG00000301465 links:

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=-0.54).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_001378924.1 link	c.-328-854A>G	intron_variant	Intron 1 of 3		NP_001365853.1
HTR2A	NM_000621.5 link	c.-743A>G	upstream_gene_variant		ENST00000542664.4	NP_000612.1	P28223-1
HTR2A	NM_001165947.5 link	c.-492A>G	upstream_gene_variant			NP_001159419.2	P28223

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 link	c.-743A>G		upstream_gene_variant		1	NM_000621.5	ENSP00000437737.1		P28223-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over