NM_000621.5:c.614-27442C>A

Variant names:

• chr13-46863081-G-T
• rs1928042
• NM_000621.5:c.614-27442C>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.614-27442C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,140 control chromosomes in the GnomAD database, including 41,684 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 0.74 (41684 hom., cov: 32)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 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.614-27442C>A		intron	N/A	NP_000612.1
	HTR2A	NM_001378924.1		c.614-27442C>A		intron	N/A	NP_001365853.1
	HTR2A	NM_001165947.5		c.125-27442C>A		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.614-27442C>A		intron	N/A	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.125-27442C>A		intron	N/A	ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112310 AN: 152022 Hom.: 41664 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.739 AC: 112374 AN: 152140 Hom.: 41684 Cov.: 32 AF XY: 0.742 AC XY: 55173 AN XY: 74370

African (AFR) AF: 0.707 AC: 29328 AN: 41488

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

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2812 AN: 3472

East Asian (EAS) AF: 0.953 AC: 4941 AN: 5186

South Asian (SAS) AF: 0.844 AC: 4064 AN: 4818

European-Finnish (FIN) AF: 0.721 AC: 7625 AN: 10572

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50255 AN: 67994

Other (OTH) AF: 0.755 AC: 1594 AN: 2112

Alfa AF: 0.744 Hom.: 54213

Bravo AF: 0.736

Asia WGS AF: 0.885 AC: 3074 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.51
PhyloP100		-0.32
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: rs1928042; hg19: chr13-47437216; COSMIC: COSV66328614;