rs543229

chrX-114586513-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000868.4(HTR2C):c.-147+1854G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.80 (24934 hom., 26307 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BS2: High Homozygotes in GnomAd at 24946 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2C	NM_000868.4	c.-147+1854G>A		intron_variant		ENST00000276198.6
HTR2C	NM_001256760.3	c.-238+1854G>A		intron_variant
HTR2C	NM_001256761.3	c.-147+1854G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2C	ENST00000276198.6	c.-147+1854G>A		intron_variant		1	NM_000868.4	P1
HTR2C	ENST00000371950.3	c.-147+1854G>A		intron_variant		1
HTR2C	ENST00000371951.5	c.-238+1854G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 88281 AN: 110317 Hom.: 24946 Cov.: 23 AF XY: 0.808 AC XY: 26280 AN XY: 32531

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.786

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.824

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.800 AC: 88287 AN: 110367 Hom.: 24934 Cov.: 23 AF XY: 0.807 AC XY: 26307 AN XY: 32591

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.983

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.824

Alfa AF: 0.823 Hom.: 28270

Bravo AF: 0.787

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs543229; hg19: chrX-113820986;