chr13-46858475-T-G

Variant names:

• chr13-46858475-T-G
• rs4942578
• NM_000621.5:c.614-22836A>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.614-22836A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,010 control chromosomes in the GnomAD database, including 40,744 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 0.72 (40744 hom., cov: 30)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 14 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.812 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.614-22836A>C		intron	N/A	NP_000612.1
	HTR2A	NM_001378924.1		c.614-22836A>C		intron	N/A	NP_001365853.1
	HTR2A	NM_001165947.5		c.125-22836A>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.614-22836A>C		intron	N/A	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.125-22836A>C		intron	N/A	ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109915 AN: 151892 Hom.: 40721 Cov.: 30

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.723 AC: 109977 AN: 152010 Hom.: 40744 Cov.: 30 AF XY: 0.721 AC XY: 53545 AN XY: 74298

African (AFR) AF: 0.572 AC: 23677 AN: 41408

American (AMR) AF: 0.693 AC: 10591 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2451 AN: 3466

East Asian (EAS) AF: 0.682 AC: 3522 AN: 5168

South Asian (SAS) AF: 0.633 AC: 3042 AN: 4806

European-Finnish (FIN) AF: 0.816 AC: 8629 AN: 10578

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55567 AN: 67988

Other (OTH) AF: 0.728 AC: 1537 AN: 2110

Alfa AF: 0.776 Hom.: 75513

Bravo AF: 0.710

Asia WGS AF: 0.623 AC: 2167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-0.15
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: rs4942578; hg19: chr13-47432610;