chr13-46855311-T-C

Variant names:

• chr13-46855311-T-C
• rs7984966
• NM_000621.5:c.614-19672A>G

Variant summary

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

The NM_000621.5(HTR2A):​c.614-19672A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,142 control chromosomes in the GnomAD database, including 5,526 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 0.25 (5526 hom., cov: 32)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 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.614-19672A>G		intron	N/A	NP_000612.1
	HTR2A	NM_001378924.1		c.614-19672A>G		intron	N/A	NP_001365853.1
	HTR2A	NM_001165947.5		c.125-19672A>G		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.614-19672A>G		intron	N/A	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.125-19672A>G		intron	N/A	ENSP00000441861.2
	HTR2A-AS1	ENST00000430913.3	TSL:3	n.313-779T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38730 AN: 152022 Hom.: 5521 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.255 AC: 38749 AN: 152142 Hom.: 5526 Cov.: 32 AF XY: 0.245 AC XY: 18202 AN XY: 74394

African (AFR) AF: 0.348 AC: 14443 AN: 41460

American (AMR) AF: 0.217 AC: 3323 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3468

East Asian (EAS) AF: 0.0494 AC: 256 AN: 5182

South Asian (SAS) AF: 0.113 AC: 546 AN: 4824

European-Finnish (FIN) AF: 0.115 AC: 1223 AN: 10608

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16863 AN: 67990

Other (OTH) AF: 0.274 AC: 580 AN: 2116

Alfa AF: 0.244 Hom.: 11031

Bravo AF: 0.269

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		-0.20
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: rs7984966; hg19: chr13-47429446; COSMIC: COSV66328298; COSMIC: COSV66328298;