rs3125

chr13-46834716-C-Gchr13-46834716-C-T

Variant summary

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

The NM_000621.5(HTR2A):c.*121G>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 0.137 in 707,280 control chromosomes in the GnomAD database, including 7,147 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 0.13 (1382 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5765 hom.)
• Consequence: HTR2A NM_000621.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_000621.5	c.*121G>C		3_prime_UTR_variant	4/4	ENST00000542664.4
HTR2A	NM_001165947.5	c.*121G>C		3_prime_UTR_variant	3/3
HTR2A	NM_001378924.1	c.*121G>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4	c.*121G>C		3_prime_UTR_variant	4/4	1	NM_000621.5	P1
HTR2A	ENST00000543956.5	c.*121G>C		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19271 AN: 152032 Hom.: 1383 Cov.: 32

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.140 AC: 77898 AN: 555132 Hom.: 5765 Cov.: 7 AF XY: 0.139 AC XY: 40180 AN XY: 289604

Gnomad4 AFR exome AF: 0.0799

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.127 AC: 19282 AN: 152148 Hom.: 1382 Cov.: 32 AF XY: 0.126 AC XY: 9404 AN XY: 74376

Gnomad4 AFR AF: 0.0802

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.143

Alfa AF: 0.0645 Hom.: 66

Bravo AF: 0.134

Asia WGS AF: 0.136 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.11
Dann	Benign	0.60

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: rs3125; hg19: chr13-47408851; COSMIC: COSV66327050;