Variant X-114584047-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The X-114584047-C-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 111,327 control chromosomes in the GnomAD database, including 762 homozygotes. There are 4,306 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.13 ( 761 hom., 4286 hem., cov: 21)

Exomes 𝑓: 0.16 ( 1 hom. 20 hem. )

Consequence

HTR2C
NM_000868.4 upstream_gene

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.695

Variant links:

Genes affected

HTR2C (HGNC:5295): (5-hydroxytryptamine receptor 2C) This gene encodes a seven-transmembrane G-protein-coupled receptor. The encoded protein responds to signaling through the neurotransmitter serotonin. The mRNA of this gene is subject to multiple RNA editing events, where adenosine residues encoded by the genome are converted to inosines. RNA editing is predicted to alter the structure of the second intracellular loop, thereby generating alternate protein forms with decreased ability to interact with G proteins. Abnormalities in RNA editing of this gene have been detected in victims of suicide that suffer from depression. In addition, naturally-occuring variation in the promoter and 5' non-coding and coding regions of this gene may show statistically-significant association with mental illness and behavioral disorders. Alternative splicing results in multiple different transcript variants. [provided by RefSeq, Jan 2015]

HTR2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-114584047-C-T is Benign according to our data. Variant chrX-114584047-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 225992.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	Effect	MANE
HTR2C	NM_000868.4 linkuse as main transcript	upstream_gene_variant	ENST00000276198.6
HTR2C	NM_001256760.3 linkuse as main transcript	upstream_gene_variant
HTR2C	NM_001256761.3 linkuse as main transcript	upstream_gene_variant

Ensembl

Gene	Transcript	Effect	TSL	MANE	Appris	UniProt
HTR2C	ENST00000276198.6 linkuse as main transcript	upstream_gene_variant	1	NM_000868.4	P1	P28335-1
HTR2C	ENST00000371950.3 linkuse as main transcript	upstream_gene_variant	1			P28335-2
HTR2C	ENST00000371951.5 linkuse as main transcript	upstream_gene_variant	1		P1	P28335-1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

14111

AN:

110991

Hom.:

762

Cov.:

AF XY:

0.129

AC XY:

4278

AN XY:

33215

show subpopulations

Gnomad AFR

AF:

0.0298

Gnomad AMI

AF:

0.0294

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.128

GnomAD4 exome

AF:

0.155

AC:

AN:

283

Hom.:

Cov.:

AF XY:

0.180

AC XY:

AN XY:

111

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.127

AC:

14116

AN:

111044

Hom.:

761

Cov.:

AF XY:

0.129

AC XY:

4286

AN XY:

33278

show subpopulations

Gnomad4 AFR

AF:

0.0299

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.148

Hom.:

3978

Bravo

AF:

0.119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

This variant is associated with the following publications: (PMID: 15741483, 17376412, 21391883, 18192901, 19106782, 20010450, 20453482, 10768099) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.0

DANN

Benign

0.93

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over