rs927544

Variant names:

• chr13-46881916-G-A
• rs927544
• NM_000621.5:c.613+10474C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-46881916-G-A
• chr13-46881916-G-C
• chr13-46881916-G-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+10474C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,066 control chromosomes in the GnomAD database, including 43,226 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 0.75 (43226 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 21 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 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+10474C>T		intron	N/A	NP_000612.1
	HTR2A	NM_001378924.1		c.613+10474C>T		intron	N/A	NP_001365853.1
	HTR2A	NM_001165947.5		c.124+10474C>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+10474C>T		intron	N/A	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.124+10474C>T		intron	N/A	ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.750 AC: 114019 AN: 151948 Hom.: 43189 Cov.: 31

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.750 AC: 114110 AN: 152066 Hom.: 43226 Cov.: 31 AF XY: 0.746 AC XY: 55432 AN XY: 74290

African (AFR) AF: 0.861 AC: 35728 AN: 41508

American (AMR) AF: 0.723 AC: 11051 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2654 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3622 AN: 5164

South Asian (SAS) AF: 0.640 AC: 3071 AN: 4798

European-Finnish (FIN) AF: 0.664 AC: 6993 AN: 10532

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.713 AC: 48481 AN: 67984

Other (OTH) AF: 0.756 AC: 1599 AN: 2114

Alfa AF: 0.723 Hom.: 70930

Bravo AF: 0.758

Asia WGS AF: 0.659 AC: 2293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.050
DANN	Benign	0.43
PhyloP100		-2.0
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: rs927544; hg19: chr13-47456051;