X-114829460-G-T

Position:

• chrX-114829460-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000868.4(HTR2C):​c.350-18543G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 106,774 control chromosomes in the GnomAD database, including 748 homozygotes. There are 3,955 hemizygotes in GnomAD. 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 0.12 (748 hom., 3955 hem., cov: 23)
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.350-18543G>T		intron_variant		ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.350-18543G>T		intron_variant			NP_001243689.2
HTR2C	NM_001256761.3	c.350-18543G>T		intron_variant			NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.350-18543G>T		intron_variant		1	NM_000868.4	ENSP00000276198	P1
HTR2C	ENST00000371950.3	c.350-18543G>T		intron_variant		1		ENSP00000361018
HTR2C	ENST00000371951.5	c.350-18543G>T		intron_variant		1		ENSP00000361019	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 13189 AN: 106722 Hom.: 746 Cov.: 23 AF XY: 0.135 AC XY: 3952 AN XY: 29188

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0506

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.124 AC: 13196 AN: 106774 Hom.: 748 Cov.: 23 AF XY: 0.135 AC XY: 3955 AN XY: 29250

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.131

Alfa AF: 0.136 Hom.: 2259

Bravo AF: 0.125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.6
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs6644093; hg19: chrX-114064023;