NM_000621.5:c.412+1050A>G

Variant names:

• chr13-46894445-T-C
• rs9534511
• NM_000621.5:c.412+1050A>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.412+1050A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,116 control chromosomes in the GnomAD database, including 23,009 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 0.54 (23009 hom., cov: 33)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 12 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]

ENSG00000301465 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 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.412+1050A>G		intron	N/A	NP_000612.1	P28223-1
	HTR2A	NM_001378924.1		c.412+1050A>G		intron	N/A	NP_001365853.1	P28223-1
	HTR2A	NM_001165947.5		c.-77-1855A>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.412+1050A>G		intron	N/A	ENSP00000437737.1	P28223-1
	HTR2A	ENST00000543956.5	TSL:1	c.-77-1855A>G		intron	N/A	ENSP00000441861.2	A0A7P0PKG8
	HTR2A	ENST00000941626.1		c.412+1050A>G		intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82575 AN: 151998 Hom.: 22993 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.543 AC: 82643 AN: 152116 Hom.: 23009 Cov.: 33 AF XY: 0.541 AC XY: 40222 AN XY: 74346

African (AFR) AF: 0.639 AC: 26504 AN: 41506

American (AMR) AF: 0.498 AC: 7613 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2185 AN: 3468

East Asian (EAS) AF: 0.643 AC: 3325 AN: 5170

South Asian (SAS) AF: 0.526 AC: 2535 AN: 4822

European-Finnish (FIN) AF: 0.432 AC: 4579 AN: 10596

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34224 AN: 67962

Other (OTH) AF: 0.589 AC: 1239 AN: 2104

Alfa AF: 0.523 Hom.: 34870

Bravo AF: 0.551

Asia WGS AF: 0.602 AC: 2093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.2
DANN	Benign	0.75
PhyloP100		-1.6
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: rs9534511; hg19: chr13-47468580; COSMIC: COSV66326908; COSMIC: COSV66326908;