chr13-46834716-C-G

Variant names:

• chr13-46834716-C-G
• rs3125
• NM_000621.5:c.*121G>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.*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
• Publications: 25 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000621.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	NM_000621.5	MANE Select	c.*121G>C		3_prime_UTR	Exon 4 of 4	NP_000612.1
	HTR2A	NM_001378924.1		c.*121G>C		3_prime_UTR	Exon 4 of 4	NP_001365853.1
	HTR2A	NM_001165947.5		c.*121G>C		3_prime_UTR	Exon 3 of 3	NP_001159419.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.*121G>C		3_prime_UTR	Exon 4 of 4	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.*121G>C		3_prime_UTR	Exon 3 of 3	ENSP00000441861.2

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

African (AFR) AF: 0.0799 AC: 1154 AN: 14452

American (AMR) AF: 0.214 AC: 4228 AN: 19730

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 1851 AN: 14432

East Asian (EAS) AF: 0.213 AC: 6943 AN: 32624

South Asian (SAS) AF: 0.120 AC: 5584 AN: 46700

European-Finnish (FIN) AF: 0.106 AC: 3661 AN: 34638

Middle Eastern (MID) AF: 0.120 AC: 403 AN: 3360

European-Non Finnish (NFE) AF: 0.139 AC: 49890 AN: 359644

Other (OTH) AF: 0.142 AC: 4184 AN: 29552

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

African (AFR) AF: 0.0802 AC: 3329 AN: 41514

American (AMR) AF: 0.188 AC: 2868 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3472

East Asian (EAS) AF: 0.175 AC: 906 AN: 5178

South Asian (SAS) AF: 0.119 AC: 574 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1159 AN: 10582

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9572 AN: 67992

Other (OTH) AF: 0.143 AC: 301 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.60
PhyloP100		0.12
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: rs3125; hg19: chr13-47408851; COSMIC: COSV66327050;