rs659734

Variant names:

• chr13-46861148-G-A
• rs659734
• NM_000621.5:c.614-25509C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-46861148-G-A
• chr13-46861148-G-C
• chr13-46861148-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-25509C>T		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.614-25509C>T		intron_variant	Intron 3 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.125-25509C>T		intron_variant	Intron 2 of 2		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-25509C>T		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.125-25509C>T		intron_variant	Intron 2 of 2	1		ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139509 AN: 152096 Hom.: 64161 Cov.: 32

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

African (AFR) AF: 0.837 AC: 34731 AN: 41496

American (AMR) AF: 0.943 AC: 14431 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3140 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5183 AN: 5186

South Asian (SAS) AF: 0.936 AC: 4516 AN: 4826

European-Finnish (FIN) AF: 0.953 AC: 10102 AN: 10604

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64438 AN: 68016

Other (OTH) AF: 0.918 AC: 1942 AN: 2116

Alfa AF: 0.927 Hom.: 111816

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
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs659734; hg19: chr13-47435283;