13-46848951-T-C

Position:

• chr13-46848951-T-C

Variant summary

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

The NM_000621.5(HTR2A):​c.614-13312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,024 control chromosomes in the GnomAD database, including 14,891 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 0.42 (14891 hom., cov: 32)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-13312A>G		intron_variant		ENST00000542664.4	NP_000612.1
HTR2A	NM_001165947.5	c.125-13312A>G		intron_variant			NP_001159419.2
HTR2A	NM_001378924.1	c.614-13312A>G		intron_variant			NP_001365853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-13312A>G		intron_variant		1	NM_000621.5	ENSP00000437737	P1
HTR2A	ENST00000543956.5	c.125-13312A>G		intron_variant		1		ENSP00000441861

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64058 AN: 151904 Hom.: 14879 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.432

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.422 AC: 64093 AN: 152024 Hom.: 14891 Cov.: 32 AF XY: 0.409 AC XY: 30428 AN XY: 74308

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.0756

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.427

Alfa AF: 0.396 Hom.: 13539

Bravo AF: 0.439

Asia WGS AF: 0.199 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.8
DANN	Benign	0.82

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: rs1923885; hg19: chr13-47423086;