13-46850677-C-T

Variant names:

• chr13-46850677-C-T
• rs1745837
• NM_000621.5:c.614-15038G>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.614-15038G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,038 control chromosomes in the GnomAD database, including 42,453 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 0.74 (42453 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 11 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 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.614-15038G>A		intron	N/A	NP_000612.1	P28223-1
	HTR2A	NM_001378924.1		c.614-15038G>A		intron	N/A	NP_001365853.1	P28223-1
	HTR2A	NM_001165947.5		c.125-15038G>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.614-15038G>A		intron	N/A	ENSP00000437737.1	P28223-1
	HTR2A	ENST00000543956.5	TSL:1	c.125-15038G>A		intron	N/A	ENSP00000441861.2	A0A7P0PKG8
	HTR2A	ENST00000941626.1		c.614-15038G>A		intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111707 AN: 151920 Hom.: 42410 Cov.: 31

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.735 AC: 111787 AN: 152038 Hom.: 42453 Cov.: 31 AF XY: 0.723 AC XY: 53705 AN XY: 74288

African (AFR) AF: 0.940 AC: 39008 AN: 41512

American (AMR) AF: 0.609 AC: 9302 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2332 AN: 3466

East Asian (EAS) AF: 0.480 AC: 2467 AN: 5142

South Asian (SAS) AF: 0.524 AC: 2524 AN: 4818

European-Finnish (FIN) AF: 0.642 AC: 6772 AN: 10556

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47115 AN: 67964

Other (OTH) AF: 0.707 AC: 1491 AN: 2108

Alfa AF: 0.674 Hom.: 16352

Bravo AF: 0.745

Asia WGS AF: 0.538 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.53
PhyloP100		-1.0
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: rs1745837; hg19: chr13-47424812; COSMIC: COSV66328273; COSMIC: COSV66328273;