13-46837850-A-G

Variant names:

• chr13-46837850-A-G
• rs7997012
• NM_000621.5:c.614-2211T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000621.5(HTR2A):​c.614-2211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,198 control chromosomes in the GnomAD database, including 37,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (37960 hom., cov: 34)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.48
• Publications: 148 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-46837850-A-G is Benign according to our data. Variant chr13-46837850-A-G is described in ClinVar as Benign. ClinVar VariationId is 226025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 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.614-2211T>C		intron	N/A	NP_000612.1
	HTR2A	NM_001378924.1		c.614-2211T>C		intron	N/A	NP_001365853.1
	HTR2A	NM_001165947.5		c.125-2211T>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.614-2211T>C		intron	N/A	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.125-2211T>C		intron	N/A	ENSP00000441861.2
	HTR2A	ENST00000941626.1		c.614-2211T>C		intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104370 AN: 152080 Hom.: 37922 Cov.: 34

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.686 AC: 104464 AN: 152198 Hom.: 37960 Cov.: 34 AF XY: 0.680 AC XY: 50595 AN XY: 74396

African (AFR) AF: 0.927 AC: 38513 AN: 41558

American (AMR) AF: 0.686 AC: 10495 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2496 AN: 3472

East Asian (EAS) AF: 0.740 AC: 3825 AN: 5168

South Asian (SAS) AF: 0.591 AC: 2852 AN: 4826

European-Finnish (FIN) AF: 0.447 AC: 4733 AN: 10582

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39323 AN: 67982

Other (OTH) AF: 0.692 AC: 1460 AN: 2110

Alfa AF: 0.625 Hom.: 62942

Bravo AF: 0.719

Asia WGS AF: 0.671 AC: 2336 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	-	Major depressive disorder, response to citalopram therapy in (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		1.5
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: rs7997012; hg19: chr13-47411985;