13-46845685-G-T

Variant names:

• chr13-46845685-G-T
• rs6561332
• NM_000621.5:c.614-10046C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000621.5(HTR2A):​c.614-10046C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 149,848 control chromosomes in the GnomAD database, including 10,800 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 0.37 (10800 hom., cov: 28)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 6 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 = 0.422 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	NM_000621.5	MANE Select	c.614-10046C>A		intron	N/A	NP_000612.1	P28223-1
	HTR2A	NM_001378924.1		c.614-10046C>A		intron	N/A	NP_001365853.1	P28223-1
	HTR2A	NM_001165947.5		c.125-10046C>A		intron	N/A	NP_001159419.2	A0A7P0PKG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.614-10046C>A		intron	N/A	ENSP00000437737.1	P28223-1
	HTR2A	ENST00000543956.5	TSL:1	c.125-10046C>A		intron	N/A	ENSP00000441861.2	A0A7P0PKG8
	HTR2A	ENST00000941626.1		c.614-10046C>A		intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55305 AN: 149756 Hom.: 10797 Cov.: 28

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.432

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.369 AC: 55325 AN: 149848 Hom.: 10800 Cov.: 28 AF XY: 0.358 AC XY: 26126 AN XY: 73042

African (AFR) AF: 0.428 AC: 17322 AN: 40508

American (AMR) AF: 0.317 AC: 4771 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1593 AN: 3460

East Asian (EAS) AF: 0.0813 AC: 417 AN: 5132

South Asian (SAS) AF: 0.264 AC: 1257 AN: 4754

European-Finnish (FIN) AF: 0.257 AC: 2567 AN: 9986

Middle Eastern (MID) AF: 0.427 AC: 122 AN: 286

European-Non Finnish (NFE) AF: 0.385 AC: 26021 AN: 67674

Other (OTH) AF: 0.391 AC: 817 AN: 2090

Alfa AF: 0.380 Hom.: 14976

Bravo AF: 0.379

Asia WGS AF: 0.198 AC: 686 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.32
PhyloP100		-0.34
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: rs6561332; hg19: chr13-47419820;