13-46897343-C-T

Variant names:

• chr13-46897343-C-T
• rs6311
• NM_001378924.1:c.-329+609G>A

Variant summary

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

The NM_001378924.1(HTR2A):​c.-329+609G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,924 control chromosomes in the GnomAD database, including 12,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.41 (12715 hom., cov: 32)
• Consequence: HTR2A NM_001378924.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2 O:1
• Conservation: PhyloP100: -2.18
• Publications: 619 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 13-46897343-C-T is Benign according to our data. Variant chr13-46897343-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 511090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_001378924.1	c.-329+609G>A		intron_variant	Intron 1 of 3		NP_001365853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000301465	ENST00000778995.1	n.111+4800C>T		intron_variant	Intron 1 of 1
ENSG00000301465	ENST00000778996.1	n.122+4739C>T		intron_variant	Intron 1 of 1
ENSG00000301465	ENST00000778997.1	n.120+1599C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61554 AN: 151806 Hom.: 12711 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.405 AC: 61590 AN: 151924 Hom.: 12715 Cov.: 32 AF XY: 0.404 AC XY: 30035 AN XY: 74258

African (AFR) AF: 0.391 AC: 16178 AN: 41402

American (AMR) AF: 0.396 AC: 6049 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1725 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3027 AN: 5154

South Asian (SAS) AF: 0.397 AC: 1908 AN: 4806

European-Finnish (FIN) AF: 0.337 AC: 3560 AN: 10552

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27846 AN: 67942

Other (OTH) AF: 0.449 AC: 947 AN: 2110

Alfa AF: 0.412 Hom.: 38982

Bravo AF: 0.408

Asia WGS AF: 0.490 AC: 1703 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Cocaine-Related Disorders Benign:1

Oct 01, 2019

Noelle C. Anastasio Laboratory, University of Texas Medical Branch

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: research

Using a Chi-squared analysis with Fisher's exact test, the allelic frequency of the rs6311 SNP (A-1438G) was not significantly different between cocaine-dependent participants versus healthy controls. -

Obsessive-compulsive disorder, susceptibility to Other:1

Sep 15, 2004

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.55
PhyloP100		-2.2
PromoterAI		0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6311; hg19: chr13-47471478;