rs643627

Positions:

• chr13-46854476-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000621.5(HTR2A):​c.614-18837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,160 control chromosomes in the GnomAD database, including 6,835 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 0.28 (6835 hom., cov: 32)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-18837A>G		intron_variant		ENST00000542664.4	NP_000612.1
HTR2A-AS1	NR_046612.1	n.231+394T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-18837A>G		intron_variant		1	NM_000621.5	ENSP00000437737	P1
HTR2A	ENST00000543956.5	c.125-18837A>G		intron_variant		1		ENSP00000441861
HTR2A-AS1	ENST00000455126.5	n.85-1614T>C		intron_variant, non_coding_transcript_variant		5
HTR2A-AS1	ENST00000430913.2	n.219+394T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42749 AN: 152042 Hom.: 6808 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.281 AC: 42807 AN: 152160 Hom.: 6835 Cov.: 32 AF XY: 0.293 AC XY: 21800 AN XY: 74368

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.301

Alfa AF: 0.295 Hom.: 2275

Bravo AF: 0.274

Asia WGS AF: 0.468 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs643627; hg19: chr13-47428611;