rs1928040

Variant names:

• chr13-46873101-G-A
• rs1928040
• NM_000621.5:c.613+19289C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-46873101-G-A
• chr13-46873101-G-C
• chr13-46873101-G-T

Variant summary

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

The NM_000621.5(HTR2A):​c.613+19289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,746 control chromosomes in the GnomAD database, including 18,570 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 0.49 (18570 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 26 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.613+19289C>T		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.613+19289C>T		intron_variant	Intron 3 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.124+19289C>T		intron_variant	Intron 2 of 2		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.613+19289C>T		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.124+19289C>T		intron_variant	Intron 2 of 2	1		ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74666 AN: 151630 Hom.: 18563 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.492 AC: 74709 AN: 151746 Hom.: 18570 Cov.: 31 AF XY: 0.496 AC XY: 36777 AN XY: 74132

African (AFR) AF: 0.512 AC: 21174 AN: 41384

American (AMR) AF: 0.498 AC: 7607 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1886 AN: 3468

East Asian (EAS) AF: 0.736 AC: 3794 AN: 5158

South Asian (SAS) AF: 0.488 AC: 2350 AN: 4816

European-Finnish (FIN) AF: 0.468 AC: 4885 AN: 10448

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.463 AC: 31442 AN: 67898

Other (OTH) AF: 0.511 AC: 1077 AN: 2108

Alfa AF: 0.479 Hom.: 29250

Bravo AF: 0.495

Asia WGS AF: 0.573 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.79
PhyloP100		-0.021
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: rs1928040; hg19: chr13-47447236;