13-46861148-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000621.5(HTR2A):​c.614-25509C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 152,214 control chromosomes in the GnomAD database, including 64,212 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 0.92 ( 64212 hom., cov: 32)

Consequence

HTR2A
NM_000621.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.554
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HTR2ANM_000621.5 linkuse as main transcriptc.614-25509C>T intron_variant ENST00000542664.4 NP_000612.1 P28223-1
HTR2ANM_001378924.1 linkuse as main transcriptc.614-25509C>T intron_variant NP_001365853.1
HTR2ANM_001165947.5 linkuse as main transcriptc.125-25509C>T intron_variant NP_001159419.2 P28223

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HTR2AENST00000542664.4 linkuse as main transcriptc.614-25509C>T intron_variant 1 NM_000621.5 ENSP00000437737.1 P28223-1
HTR2AENST00000543956.5 linkuse as main transcriptc.125-25509C>T intron_variant 1 ENSP00000441861.2 A0A7P0PKG8

Frequencies

GnomAD3 genomes
AF:
0.917
AC:
139509
AN:
152096
Hom.:
64161
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.837
Gnomad AMI
AF:
0.946
Gnomad AMR
AF:
0.943
Gnomad ASJ
AF:
0.905
Gnomad EAS
AF:
0.999
Gnomad SAS
AF:
0.936
Gnomad FIN
AF:
0.953
Gnomad MID
AF:
0.927
Gnomad NFE
AF:
0.947
Gnomad OTH
AF:
0.917
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.917
AC:
139618
AN:
152214
Hom.:
64212
Cov.:
32
AF XY:
0.919
AC XY:
68406
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.837
Gnomad4 AMR
AF:
0.943
Gnomad4 ASJ
AF:
0.905
Gnomad4 EAS
AF:
0.999
Gnomad4 SAS
AF:
0.936
Gnomad4 FIN
AF:
0.953
Gnomad4 NFE
AF:
0.947
Gnomad4 OTH
AF:
0.918
Alfa
AF:
0.938
Hom.:
65728
Bravo
AF:
0.913
Asia WGS
AF:
0.962
AC:
3343
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
4.7
DANN
Benign
0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs659734; hg19: chr13-47435283; API