chr13-46897755-G-A

Variant names:

• chr13-46897755-G-A
• rs1328685
• NM_001378924.1:c.-329+197C>T

Variant summary

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

The NM_001378924.1(HTR2A):​c.-329+197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,178 control chromosomes in the GnomAD database, including 57,332 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 0.87 (57332 hom., cov: 31)
• Consequence: HTR2A NM_001378924.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 15 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378924.1. 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_001378924.1		c.-329+197C>T		intron	N/A	NP_001365853.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000301465	ENST00000778995.1		n.111+5212G>A		intron	N/A
	ENSG00000301465	ENST00000778996.1		n.122+5151G>A		intron	N/A
	ENSG00000301465	ENST00000778997.1		n.120+2011G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131652 AN: 152060 Hom.: 57286 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.866 AC: 131753 AN: 152178 Hom.: 57332 Cov.: 31 AF XY: 0.868 AC XY: 64581 AN XY: 74386

African (AFR) AF: 0.762 AC: 31611 AN: 41490

American (AMR) AF: 0.894 AC: 13676 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2958 AN: 3472

East Asian (EAS) AF: 0.958 AC: 4959 AN: 5176

South Asian (SAS) AF: 0.916 AC: 4415 AN: 4820

European-Finnish (FIN) AF: 0.917 AC: 9715 AN: 10592

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61522 AN: 68006

Other (OTH) AF: 0.859 AC: 1816 AN: 2114

Alfa AF: 0.885 Hom.: 86621

Bravo AF: 0.858

Asia WGS AF: 0.932 AC: 3241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.062
DANN	Benign	0.20
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1328685; hg19: chr13-47471890;