rs6316

Positions:

• chr13-46897088-T-C

Variant summary

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

The NM_001378924.1(HTR2A):​c.-328-854A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 440,608 control chromosomes in the GnomAD database, including 220 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 0.027 (189 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (31 hom.)
• Consequence: HTR2A NM_001378924.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_001378924.1	c.-328-854A>G		intron_variant
HTR2A	NM_000621.5			upstream_gene_variant		ENST00000542664.4
HTR2A	NM_001165947.5			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4			upstream_gene_variant		1	NM_000621.5	P1
HTR2A	ENST00000543956.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4180 AN: 152140 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00323 AC: 932 AN: 288350 Hom.: 31 Cov.: 0 AF XY: 0.00281 AC XY: 423 AN XY: 150414

Gnomad4 AFR exome AF: 0.0984

Gnomad4 AMR exome AF: 0.00705

Gnomad4 ASJ exome AF: 0.000104

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000126

Gnomad4 OTH exome AF: 0.00750

GnomAD4 genome AF: 0.0275 AC: 4185 AN: 152258 Hom.: 189 Cov.: 32 AF XY: 0.0268 AC XY: 1996 AN XY: 74456

Gnomad4 AFR AF: 0.0965

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0327 Hom.: 30

Bravo AF: 0.0311

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6316; hg19: chr13-47471223;