chr13-46881728-A-G

Variant names:

• chr13-46881728-A-G
• rs985933
• NM_000621.5:c.613+10662T>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.613+10662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,990 control chromosomes in the GnomAD database, including 26,838 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 0.59 (26838 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 20 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 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.613+10662T>C		intron	N/A	NP_000612.1
	HTR2A	NM_001378924.1		c.613+10662T>C		intron	N/A	NP_001365853.1
	HTR2A	NM_001165947.5		c.124+10662T>C		intron	N/A	NP_001159419.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.613+10662T>C		intron	N/A	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.124+10662T>C		intron	N/A	ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90059 AN: 151872 Hom.: 26820 Cov.: 31

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.593 AC: 90120 AN: 151990 Hom.: 26838 Cov.: 31 AF XY: 0.592 AC XY: 43950 AN XY: 74288

African (AFR) AF: 0.536 AC: 22210 AN: 41444

American (AMR) AF: 0.605 AC: 9234 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2212 AN: 3472

East Asian (EAS) AF: 0.667 AC: 3431 AN: 5146

South Asian (SAS) AF: 0.562 AC: 2700 AN: 4806

European-Finnish (FIN) AF: 0.581 AC: 6148 AN: 10576

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 42127 AN: 67970

Other (OTH) AF: 0.602 AC: 1270 AN: 2110

Alfa AF: 0.609 Hom.: 18199

Bravo AF: 0.590

Asia WGS AF: 0.592 AC: 2059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		0.058
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: rs985933; hg19: chr13-47455863;