13-46856141-C-G

Position:

• chr13-46856141-C-G

Variant summary

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

The NM_000621.5(HTR2A):​c.614-20502G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,104 control chromosomes in the GnomAD database, including 7,756 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 0.32 (7756 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315

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]

HTR2A-AS1 (HGNC:40289): (HTR2A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_000621.5	c.614-20502G>C		intron_variant		ENST00000542664.4
HTR2A-AS1	NR_046612.1	n.283C>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-20502G>C		intron_variant		1	NM_000621.5	P1
HTR2A	ENST00000543956.5	c.125-20502G>C		intron_variant		1
HTR2A-AS1	ENST00000455126.5	n.136C>G		non_coding_transcript_exon_variant	2/2	5
HTR2A-AS1	ENST00000430913.2	n.271C>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48242 AN: 151980 Hom.: 7747 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.317 AC: 48253 AN: 152098 Hom.: 7756 Cov.: 32 AF XY: 0.315 AC XY: 23398 AN XY: 74364

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.320

Alfa AF: 0.198 Hom.: 431

Bravo AF: 0.312

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1885884; hg19: chr13-47430276;