13-46896689-C-T

Variant names:

• chr13-46896689-C-T
• rs6312
• NM_000621.5:c.-344G>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.-344G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.94 in 1,532,638 control chromosomes in the GnomAD database, including 677,813 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 0.92 (64069 hom., cov: 33)
  • Exomes 𝑓: 0.94 (613744 hom.)
• Consequence: HTR2A NM_000621.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91
• Publications: 32 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]

ENSG00000301465 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.908041E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.-344G>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001165947.5	c.-93G>A		5_prime_UTR_variant	Exon 1 of 3		NP_001159419.2
HTR2A	NM_001378924.1	c.-328-455G>A		intron_variant	Intron 1 of 3		NP_001365853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.-344G>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_000621.5	ENSP00000437737.1

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139397 AN: 152184 Hom.: 64023 Cov.: 33

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.923

GnomAD2 exomes AF: 0.941 AC: 130771 AN: 139004 AF XY: 0.940

Gnomad AFR exome AF: 0.830

Gnomad AMR exome AF: 0.965

Gnomad ASJ exome AF: 0.907

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.956

Gnomad NFE exome AF: 0.944

Gnomad OTH exome AF: 0.933

GnomAD4 exome AF: 0.943 AC: 1301210 AN: 1380336 Hom.: 613744 Cov.: 32 AF XY: 0.942 AC XY: 641736 AN XY: 681080

African (AFR) AF: 0.830 AC: 26026 AN: 31372

American (AMR) AF: 0.962 AC: 33507 AN: 34818

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 22723 AN: 25096

East Asian (EAS) AF: 1.00 AC: 35584 AN: 35590

South Asian (SAS) AF: 0.928 AC: 72845 AN: 78460

European-Finnish (FIN) AF: 0.951 AC: 33279 AN: 34986

Middle Eastern (MID) AF: 0.882 AC: 5011 AN: 5682

European-Non Finnish (NFE) AF: 0.946 AC: 1018491 AN: 1076600

Other (OTH) AF: 0.931 AC: 53744 AN: 57732

GnomAD4 genome AF: 0.916 AC: 139497 AN: 152302 Hom.: 64069 Cov.: 33 AF XY: 0.918 AC XY: 68327 AN XY: 74468

African (AFR) AF: 0.835 AC: 34696 AN: 41542

American (AMR) AF: 0.947 AC: 14494 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3145 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5185 AN: 5188

South Asian (SAS) AF: 0.926 AC: 4475 AN: 4832

European-Finnish (FIN) AF: 0.952 AC: 10100 AN: 10614

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64313 AN: 68032

Other (OTH) AF: 0.923 AC: 1954 AN: 2116

Alfa AF: 0.935 Hom.: 232094

Bravo AF: 0.912

TwinsUK AF: 0.950 AC: 3522

ALSPAC AF: 0.953 AC: 3671

ESP6500AA AF: 0.830 AC: 1149

ESP6500EA AF: 0.934 AC: 2971

ExAC AF: 0.915 AC: 17495

Asia WGS AF: 0.960 AC: 3340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.96
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.48	T
MetaRNN	Benign	9.9e-7	T
MetaSVM	Benign	-0.99	T
PhyloP100		4.9
PROVEAN	Benign	0.94	N
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Vest4		0.15
ClinPred		0.059	T
GERP RS		4.5
PromoterAI		-0.19	Neutral
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6312; hg19: chr13-47470824; COSMIC: COSV107496256; COSMIC: COSV107496256;