rs3803189

Positions:

• chr13-46834435-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000621.5(HTR2A):​c.*402A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 161,338 control chromosomes in the GnomAD database, including 2,910 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 0.18 (2812 hom., cov: 32)
  • Exomes 𝑓: 0.13 (98 hom.)
• Consequence: HTR2A NM_000621.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_000621.5	c.*402A>C		3_prime_UTR_variant	4/4	ENST00000542664.4
HTR2A	NM_001165947.5	c.*402A>C		3_prime_UTR_variant	3/3
HTR2A	NM_001378924.1	c.*402A>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4	c.*402A>C		3_prime_UTR_variant	4/4	1	NM_000621.5	P1
HTR2A	ENST00000543956.5	c.*402A>C		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27536 AN: 151960 Hom.: 2817 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.131 AC: 1213 AN: 9260 Hom.: 98 Cov.: 0 AF XY: 0.132 AC XY: 636 AN XY: 4828

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0836

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.181 AC: 27548 AN: 152078 Hom.: 2812 Cov.: 32 AF XY: 0.179 AC XY: 13312 AN XY: 74352

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.180

Alfa AF: 0.156 Hom.: 1437

Bravo AF: 0.197

Asia WGS AF: 0.144 AC: 503 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs3803189; hg19: chr13-47408570;