chr13-46849156-C-T

Variant names:

• chr13-46849156-C-T
• rs1923886
• NM_000621.5:c.614-13517G>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.614-13517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,126 control chromosomes in the GnomAD database, including 33,321 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 0.64 (33321 hom., cov: 32)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-13517G>A		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.614-13517G>A		intron_variant	Intron 3 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.125-13517G>A		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.614-13517G>A		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.125-13517G>A		intron_variant	Intron 2 of 2	1		ENSP00000441861.2
HTR2A-AS1	ENST00000430913.3	n.87-2989C>T		intron_variant	Intron 1 of 3	3
HTR2A-AS1	ENST00000452352.6	n.87-2989C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.638 AC: 97001 AN: 152008 Hom.: 33289 Cov.: 32

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.638 AC: 97072 AN: 152126 Hom.: 33321 Cov.: 32 AF XY: 0.627 AC XY: 46620 AN XY: 74344

African (AFR) AF: 0.910 AC: 37819 AN: 41540

American (AMR) AF: 0.560 AC: 8567 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2162 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2593 AN: 5160

South Asian (SAS) AF: 0.478 AC: 2303 AN: 4814

European-Finnish (FIN) AF: 0.426 AC: 4495 AN: 10564

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.545 AC: 37037 AN: 67968

Other (OTH) AF: 0.629 AC: 1330 AN: 2114

Alfa AF: 0.569 Hom.: 15117

Bravo AF: 0.663

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.41
PhyloP100		-0.18
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: rs1923886; hg19: chr13-47423291;