rs543229

Variant names:

• chrX-114586513-G-A
• rs543229
• NM_000868.4:c.-147+1854G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

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
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-147+1854G>A		intron_variant	Intron 1 of 5	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-238+1854G>A		intron_variant	Intron 1 of 6		NP_001243689.2
HTR2C	NM_001256761.3	c.-147+1854G>A		intron_variant	Intron 1 of 5		NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-147+1854G>A		intron_variant	Intron 1 of 5	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.-238+1854G>A		intron_variant	Intron 1 of 6	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.-147+1854G>A		intron_variant	Intron 1 of 5	1		ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.800 AC: 88281 AN: 110317 Hom.: 24946 Cov.: 23

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

African (AFR) AF: 0.699 AC: 21220 AN: 30341

American (AMR) AF: 0.807 AC: 8367 AN: 10369

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2068 AN: 2639

East Asian (EAS) AF: 0.983 AC: 3431 AN: 3489

South Asian (SAS) AF: 0.886 AC: 2243 AN: 2533

European-Finnish (FIN) AF: 0.883 AC: 5116 AN: 5794

Middle Eastern (MID) AF: 0.758 AC: 160 AN: 211

European-Non Finnish (NFE) AF: 0.831 AC: 43896 AN: 52818

Other (OTH) AF: 0.824 AC: 1235 AN: 1499

Alfa AF: 0.803 Hom.: 43400

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
PhyloP100		2.4

Splicing

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

Other links and lift over

dbSNP: rs543229; hg19: chrX-113820986;