rs12833104

Positions:

• chrX-114690182-G-A
• chrX-114690182-G-C

Variant summary

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

The ENST00000276198.6(HTR2C):​c.-79-36676G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 110,770 control chromosomes in the GnomAD database, including 946 homozygotes. There are 4,652 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 0.14 (946 hom., 4652 hem., cov: 22)
• Consequence: HTR2C ENST00000276198.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-79-36676G>A		intron_variant		ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-170-27404G>A		intron_variant			NP_001243689.2
HTR2C	NM_001256761.3	c.-79-36676G>A		intron_variant			NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-79-36676G>A		intron_variant		1	NM_000868.4	ENSP00000276198	P1
HTR2C	ENST00000371950.3	c.-79-36676G>A		intron_variant		1		ENSP00000361018
HTR2C	ENST00000371951.5	c.-170-27404G>A		intron_variant		1		ENSP00000361019	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 15381 AN: 110715 Hom.: 944 Cov.: 22 AF XY: 0.141 AC XY: 4641 AN XY: 32959

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0321

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.139 AC: 15395 AN: 110770 Hom.: 946 Cov.: 22 AF XY: 0.141 AC XY: 4652 AN XY: 33024

Gnomad4 AFR AF: 0.0271

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.146

Alfa AF: 0.164 Hom.: 1622

Bravo AF: 0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.026
DANN	Benign	0.46

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: rs12833104; hg19: chrX-113924660;