NM_000621.5:c.614-9430T>C

Variant names:

• chr13-46845069-A-G
• rs9567735
• NM_000621.5:c.614-9430T>C

Variant summary

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

The NM_000621.5(HTR2A):​c.614-9430T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,070 control chromosomes in the GnomAD database, including 2,005 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 0.14 (2005 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-9430T>C		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.614-9430T>C		intron_variant	Intron 3 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.125-9430T>C		intron_variant	Intron 2 of 2		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-9430T>C		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21681 AN: 151952 Hom.: 2010 Cov.: 31

Gnomad AFR AF: 0.0958

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.143 AC: 21678 AN: 152070 Hom.: 2005 Cov.: 31 AF XY: 0.146 AC XY: 10886 AN XY: 74328

African (AFR) AF: 0.0958 AC: 3973 AN: 41490

American (AMR) AF: 0.176 AC: 2685 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.479 AC: 2478 AN: 5168

South Asian (SAS) AF: 0.183 AC: 882 AN: 4812

European-Finnish (FIN) AF: 0.147 AC: 1550 AN: 10558

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9130 AN: 67984

Other (OTH) AF: 0.150 AC: 317 AN: 2112

Alfa AF: 0.136 Hom.: 201

Bravo AF: 0.145

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.30
DANN	Benign	0.42
PhyloP100		-0.42
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: rs9567735; hg19: chr13-47419204;