X-114892616-T-C

Position:

• chrX-114892616-T-C

Variant summary

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

The NM_000868.4(HTR2C):​c.551-13973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 110,840 control chromosomes in the GnomAD database, including 72 homozygotes. There are 1,229 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 0.038 (72 hom., 1229 hem., cov: 23)
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2C	NM_000868.4	c.551-13973T>C		intron_variant		ENST00000276198.6
HTR2C	NM_001256760.3	c.551-13973T>C		intron_variant
HTR2C	NM_001256761.3	c.456-13973T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2C	ENST00000276198.6	c.551-13973T>C		intron_variant		1	NM_000868.4	P1
HTR2C	ENST00000371950.3	c.456-13973T>C		intron_variant		1
HTR2C	ENST00000371951.5	c.551-13973T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 4167 AN: 110810 Hom.: 72 Cov.: 23 AF XY: 0.0373 AC XY: 1233 AN XY: 33094

Gnomad AFR AF: 0.00695

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0409

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0451

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

GnomAD4 genome AF: 0.0376 AC: 4163 AN: 110840 Hom.: 72 Cov.: 23 AF XY: 0.0371 AC XY: 1229 AN XY: 33136

Gnomad4 AFR AF: 0.00694

Gnomad4 AMR AF: 0.0275

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0914

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.0452

Alfa AF: 0.0499 Hom.: 765

Bravo AF: 0.0370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.62

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: rs10875535; hg19: chrX-114127179;