chr13-46859220-C-G

Position:

• chr13-46859220-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000621.5(HTR2A):​c.614-23581G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,914 control chromosomes in the GnomAD database, including 5,295 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 0.25 (5295 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-23581G>C		intron_variant		ENST00000542664.4	NP_000612.1
HTR2A	NM_001165947.5	c.125-23581G>C		intron_variant			NP_001159419.2
HTR2A	NM_001378924.1	c.614-23581G>C		intron_variant			NP_001365853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-23581G>C		intron_variant		1	NM_000621.5	ENSP00000437737	P1
HTR2A	ENST00000543956.5	c.125-23581G>C		intron_variant		1		ENSP00000441861

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38061 AN: 151796 Hom.: 5278 Cov.: 31

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.251 AC: 38114 AN: 151914 Hom.: 5295 Cov.: 31 AF XY: 0.253 AC XY: 18809 AN XY: 74248

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.258

Alfa AF: 0.0937 Hom.: 112

Bravo AF: 0.263

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.065
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs9316233; hg19: chr13-47433355;