rs1923882

Variant names:

• chr13-46837526-C-T
• rs1923882
• NM_000621.5:c.614-1887G>A

Variant summary

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

The NM_000621.5(HTR2A):​c.614-1887G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,072 control chromosomes in the GnomAD database, including 5,557 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 0.26 (5557 hom., cov: 32)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 15 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-1887G>A		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.614-1887G>A		intron_variant	Intron 3 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.125-1887G>A		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.614-1887G>A		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.125-1887G>A		intron_variant	Intron 2 of 2	1		ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39891 AN: 151954 Hom.: 5549 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.263 AC: 39936 AN: 152072 Hom.: 5557 Cov.: 32 AF XY: 0.260 AC XY: 19309 AN XY: 74314

African (AFR) AF: 0.352 AC: 14594 AN: 41456

American (AMR) AF: 0.277 AC: 4229 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3468

East Asian (EAS) AF: 0.177 AC: 914 AN: 5166

South Asian (SAS) AF: 0.239 AC: 1154 AN: 4824

European-Finnish (FIN) AF: 0.162 AC: 1719 AN: 10582

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15675 AN: 67976

Other (OTH) AF: 0.266 AC: 562 AN: 2110

Alfa AF: 0.255 Hom.: 1101

Bravo AF: 0.276

Asia WGS AF: 0.208 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.31
DANN	Benign	0.46
PhyloP100		-1.2
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: rs1923882; hg19: chr13-47411661;