chrX-114662932-G-C

Variant names:

• chrX-114662932-G-C
• rs12858300
• NM_000868.4:c.-80+49051G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000868.4(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 NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.600
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000868.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	NM_000868.4	MANE Select	c.-80+49051G>C		intron	N/A	NP_000859.2
	HTR2C	NM_001256760.3		c.-171+49051G>C		intron	N/A	NP_001243689.2
	HTR2C	NM_001256761.3		c.-80+49051G>C		intron	N/A	NP_001243690.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	ENST00000276198.6	TSL:1 MANE Select	c.-80+49051G>C		intron	N/A	ENSP00000276198.1
	HTR2C	ENST00000371951.5	TSL:1	c.-171+49051G>C		intron	N/A	ENSP00000361019.1
	HTR2C	ENST00000371950.3	TSL:1	c.-80+49051G>C		intron	N/A	ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 4415 AN: 111699 Hom.: 77 Cov.: 23

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

African (AFR) AF: 0.00709 AC: 219 AN: 30877

American (AMR) AF: 0.0290 AC: 305 AN: 10504

Ashkenazi Jewish (ASJ) AF: 0.0685 AC: 181 AN: 2642

East Asian (EAS) AF: 0.0212 AC: 75 AN: 3544

South Asian (SAS) AF: 0.0511 AC: 138 AN: 2703

European-Finnish (FIN) AF: 0.0281 AC: 170 AN: 6050

Middle Eastern (MID) AF: 0.0326 AC: 7 AN: 215

European-Non Finnish (NFE) AF: 0.0612 AC: 3243 AN: 53007

Other (OTH) AF: 0.0434 AC: 66 AN: 1519

Alfa AF: 0.0509 Hom.: 291

Bravo AF: 0.0372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12858300; hg19: chrX-113897413;