NM_000621.5:c.614-13791T>A

Variant names:

• chr13-46849430-A-T
• rs7330461
• NM_000621.5:c.614-13791T>A

Variant summary

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

The NM_000621.5(HTR2A):​c.614-13791T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,896 control chromosomes in the GnomAD database, including 12,443 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 0.39 (12443 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• Publications: 8 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]

HTR2A-AS1 (HGNC:40289): (HTR2A antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 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.614-13791T>A		intron	N/A	NP_000612.1
	HTR2A	NM_001378924.1		c.614-13791T>A		intron	N/A	NP_001365853.1
	HTR2A	NM_001165947.5		c.125-13791T>A		intron	N/A	NP_001159419.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.614-13791T>A		intron	N/A	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.125-13791T>A		intron	N/A	ENSP00000441861.2
	HTR2A	ENST00000941626.1		c.614-13791T>A		intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58581 AN: 151778 Hom.: 12436 Cov.: 31

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.386 AC: 58606 AN: 151896 Hom.: 12443 Cov.: 31 AF XY: 0.373 AC XY: 27715 AN XY: 74214

African (AFR) AF: 0.547 AC: 22665 AN: 41416

American (AMR) AF: 0.310 AC: 4730 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1503 AN: 3468

East Asian (EAS) AF: 0.0742 AC: 383 AN: 5162

South Asian (SAS) AF: 0.174 AC: 836 AN: 4814

European-Finnish (FIN) AF: 0.257 AC: 2715 AN: 10546

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24430 AN: 67920

Other (OTH) AF: 0.390 AC: 821 AN: 2104

Alfa AF: 0.143 Hom.: 213

Bravo AF: 0.401

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-0.37
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: rs7330461; hg19: chr13-47423565;