chr13-46871568-G-A

Variant names:

• chr13-46871568-G-A
• rs9316235
• NM_000621.5:c.613+20822C>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+20822C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,064 control chromosomes in the GnomAD database, including 3,508 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 0.20 (3508 hom., cov: 33)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.942
• Publications: 7 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	NM_000621.5	MANE Select	c.613+20822C>T		intron	N/A	NP_000612.1
	HTR2A	NM_001378924.1		c.613+20822C>T		intron	N/A	NP_001365853.1
	HTR2A	NM_001165947.5		c.124+20822C>T		intron	N/A	NP_001159419.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.613+20822C>T		intron	N/A	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.124+20822C>T		intron	N/A	ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30202 AN: 151946 Hom.: 3501 Cov.: 33

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.199 AC: 30226 AN: 152064 Hom.: 3508 Cov.: 33 AF XY: 0.200 AC XY: 14875 AN XY: 74344

African (AFR) AF: 0.0786 AC: 3259 AN: 41476

American (AMR) AF: 0.187 AC: 2853 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 685 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1113 AN: 5178

South Asian (SAS) AF: 0.347 AC: 1667 AN: 4808

European-Finnish (FIN) AF: 0.251 AC: 2650 AN: 10554

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17440 AN: 67972

Other (OTH) AF: 0.195 AC: 412 AN: 2112

Alfa AF: 0.234 Hom.: 3081

Bravo AF: 0.187

Asia WGS AF: 0.300 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.8
DANN	Benign	0.65
PhyloP100		0.94
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: rs9316235; hg19: chr13-47445703;