13-46877151-T-C

Variant names:

• chr13-46877151-T-C
• rs912127
• NM_000621.5:c.613+15239A>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.613+15239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,114 control chromosomes in the GnomAD database, including 49,096 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 0.80 (49096 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 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+15239A>G		intron	N/A	NP_000612.1	P28223-1
	HTR2A	NM_001378924.1		c.613+15239A>G		intron	N/A	NP_001365853.1	P28223-1
	HTR2A	NM_001165947.5		c.124+15239A>G		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+15239A>G		intron	N/A	ENSP00000437737.1	P28223-1
	HTR2A	ENST00000543956.5	TSL:1	c.124+15239A>G		intron	N/A	ENSP00000441861.2	A0A7P0PKG8
	HTR2A	ENST00000941626.1		c.613+15239A>G		intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121597 AN: 151996 Hom.: 49061 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.800 AC: 121684 AN: 152114 Hom.: 49096 Cov.: 31 AF XY: 0.796 AC XY: 59197 AN XY: 74356

African (AFR) AF: 0.911 AC: 37819 AN: 41532

American (AMR) AF: 0.789 AC: 12059 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2928 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3739 AN: 5150

South Asian (SAS) AF: 0.732 AC: 3507 AN: 4794

European-Finnish (FIN) AF: 0.717 AC: 7578 AN: 10572

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51403 AN: 67986

Other (OTH) AF: 0.809 AC: 1711 AN: 2114

Alfa AF: 0.783 Hom.: 6054

Bravo AF: 0.808

Asia WGS AF: 0.733 AC: 2549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.65
DANN	Benign	0.38
PhyloP100		-1.1
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: rs912127; hg19: chr13-47451286;