rs9534505

Variant names:

• chr13-46886609-A-G
• rs9534505
• NM_000621.5:c.613+5781T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-46886609-A-G
• chr13-46886609-A-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.613+5781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,122 control chromosomes in the GnomAD database, including 58,689 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 0.88 (58689 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.613+5781T>C		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.613+5781T>C		intron_variant	Intron 3 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.124+5781T>C		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.613+5781T>C		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.124+5781T>C		intron_variant	Intron 2 of 2	1		ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133306 AN: 152004 Hom.: 58649 Cov.: 31

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.874

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.877 AC: 133404 AN: 152122 Hom.: 58689 Cov.: 31 AF XY: 0.878 AC XY: 65291 AN XY: 74374

African (AFR) AF: 0.794 AC: 32932 AN: 41452

American (AMR) AF: 0.907 AC: 13857 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3069 AN: 3470

East Asian (EAS) AF: 0.951 AC: 4930 AN: 5186

South Asian (SAS) AF: 0.889 AC: 4265 AN: 4800

European-Finnish (FIN) AF: 0.913 AC: 9673 AN: 10596

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61716 AN: 68014

Other (OTH) AF: 0.872 AC: 1846 AN: 2116

Alfa AF: 0.898 Hom.: 103700

Bravo AF: 0.872

Asia WGS AF: 0.903 AC: 3140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.82
PhyloP100		0.22
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: rs9534505; hg19: chr13-47460744;