chr13-46871832-A-C

Variant names:

• chr13-46871832-A-C
• rs9526245
• NM_000621.5:c.613+20558T>G

Variant summary

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

The NM_000621.5(HTR2A):​c.613+20558T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,126 control chromosomes in the GnomAD database, including 3,503 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 0.20 (3503 hom., cov: 33)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 7 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=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.613+20558T>G		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.613+20558T>G		intron_variant	Intron 3 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.124+20558T>G		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.613+20558T>G		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.124+20558T>G		intron_variant	Intron 2 of 2	1		ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30191 AN: 152006 Hom.: 3496 Cov.: 33

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.199 AC: 30215 AN: 152126 Hom.: 3503 Cov.: 33 AF XY: 0.200 AC XY: 14864 AN XY: 74372

African (AFR) AF: 0.0788 AC: 3274 AN: 41550

American (AMR) AF: 0.187 AC: 2850 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 685 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1101 AN: 5162

South Asian (SAS) AF: 0.346 AC: 1664 AN: 4812

European-Finnish (FIN) AF: 0.250 AC: 2643 AN: 10570

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17438 AN: 67968

Other (OTH) AF: 0.195 AC: 413 AN: 2114

Alfa AF: 0.213 Hom.: 647

Bravo AF: 0.187

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.1
DANN	Benign	0.85
PhyloP100		-0.35
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: rs9526245; hg19: chr13-47445967;