rs12858300

Positions:

• chrX-114662932-G-C

Variant summary

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

The ENST00000276198.6(HTR2C):​c.-80+49051G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 111,749 control chromosomes in the GnomAD database, including 77 homozygotes. There are 1,265 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 0.040 (77 hom., 1265 hem., cov: 23)
• Consequence: HTR2C ENST00000276198.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.600

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-80+49051G>C		intron_variant		ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-171+49051G>C		intron_variant			NP_001243689.2
HTR2C	NM_001256761.3	c.-80+49051G>C		intron_variant			NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-80+49051G>C		intron_variant		1	NM_000868.4	ENSP00000276198	P1
HTR2C	ENST00000371950.3	c.-80+49051G>C		intron_variant		1		ENSP00000361018
HTR2C	ENST00000371951.5	c.-171+49051G>C		intron_variant		1		ENSP00000361019	P1

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 4415 AN: 111699 Hom.: 77 Cov.: 23 AF XY: 0.0373 AC XY: 1263 AN XY: 33883

Gnomad AFR AF: 0.00711

Gnomad AMI AF: 0.0174

Gnomad AMR AF: 0.0291

Gnomad ASJ AF: 0.0685

Gnomad EAS AF: 0.0211

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.0299

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0420

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

GnomAD4 genome AF: 0.0395 AC: 4416 AN: 111749 Hom.: 77 Cov.: 23 AF XY: 0.0373 AC XY: 1265 AN XY: 33943

Gnomad4 AFR AF: 0.00709

Gnomad4 AMR AF: 0.0290

Gnomad4 ASJ AF: 0.0685

Gnomad4 EAS AF: 0.0212

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.0612

Gnomad4 OTH AF: 0.0434

Alfa AF: 0.0509 Hom.: 291

Bravo AF: 0.0372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.51

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: rs12858300; hg19: chrX-113897413;