13-46840866-A-C

Variant names:

• chr13-46840866-A-C
• rs977003
• NM_000621.5:c.614-5227T>G

Variant summary

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

The NM_000621.5(HTR2A):​c.614-5227T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,994 control chromosomes in the GnomAD database, including 23,453 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 0.53 (23453 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 26 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 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.614-5227T>G		intron	N/A	NP_000612.1
	HTR2A	NM_001378924.1		c.614-5227T>G		intron	N/A	NP_001365853.1
	HTR2A	NM_001165947.5		c.125-5227T>G		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.614-5227T>G		intron	N/A	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.125-5227T>G		intron	N/A	ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79941 AN: 151876 Hom.: 23415 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.527 AC: 80036 AN: 151994 Hom.: 23453 Cov.: 31 AF XY: 0.516 AC XY: 38305 AN XY: 74302

African (AFR) AF: 0.785 AC: 32555 AN: 41446

American (AMR) AF: 0.492 AC: 7506 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2008 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1182 AN: 5172

South Asian (SAS) AF: 0.369 AC: 1774 AN: 4812

European-Finnish (FIN) AF: 0.299 AC: 3170 AN: 10588

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30142 AN: 67926

Other (OTH) AF: 0.526 AC: 1112 AN: 2114

Alfa AF: 0.462 Hom.: 26201

Bravo AF: 0.556

Asia WGS AF: 0.322 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.52
PhyloP100		-1.5
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: rs977003; hg19: chr13-47415001;