13-46871859-A-G

Variant names:

• chr13-46871859-A-G
• rs582385
• NM_000621.5:c.613+20531T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000621.5(HTR2A):​c.613+20531T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,228 control chromosomes in the GnomAD database, including 2,764 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 0.18 (2764 hom., cov: 33)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.842
• Publications: 19 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000621.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	NM_000621.5	MANE Select	c.613+20531T>C		intron	N/A	NP_000612.1	P28223-1
	HTR2A	NM_001378924.1		c.613+20531T>C		intron	N/A	NP_001365853.1	P28223-1
	HTR2A	NM_001165947.5		c.124+20531T>C		intron	N/A	NP_001159419.2	A0A7P0PKG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.613+20531T>C		intron	N/A	ENSP00000437737.1	P28223-1
	HTR2A	ENST00000543956.5	TSL:1	c.124+20531T>C		intron	N/A	ENSP00000441861.2	A0A7P0PKG8
	HTR2A	ENST00000941626.1		c.613+20531T>C		intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27994 AN: 152110 Hom.: 2754 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.184 AC: 28038 AN: 152228 Hom.: 2764 Cov.: 33 AF XY: 0.181 AC XY: 13473 AN XY: 74436

African (AFR) AF: 0.191 AC: 7916 AN: 41540

American (AMR) AF: 0.209 AC: 3196 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3470

East Asian (EAS) AF: 0.0160 AC: 83 AN: 5188

South Asian (SAS) AF: 0.0960 AC: 463 AN: 4822

European-Finnish (FIN) AF: 0.201 AC: 2133 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13051 AN: 68008

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.184 Hom.: 8892

Bravo AF: 0.186

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.84
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: rs582385; hg19: chr13-47445994;