rs498177

Positions:

• chrX-114590222-G-A

Variant summary

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

The NM_000868.4(HTR2C):​c.-147+5563G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 110,673 control chromosomes in the GnomAD database, including 11,204 homozygotes. There are 15,956 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 0.48 (11204 hom., 15956 hem., cov: 23)
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-147+5563G>A		intron_variant		ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-238+5563G>A		intron_variant			NP_001243689.2
HTR2C	NM_001256761.3	c.-147+5563G>A		intron_variant			NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-147+5563G>A		intron_variant		1	NM_000868.4	ENSP00000276198	P1
HTR2C	ENST00000371950.3	c.-147+5563G>A		intron_variant		1		ENSP00000361018
HTR2C	ENST00000371951.5	c.-238+5563G>A		intron_variant		1		ENSP00000361019	P1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 53176 AN: 110616 Hom.: 11217 Cov.: 23 AF XY: 0.485 AC XY: 15951 AN XY: 32890

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.543

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.480 AC: 53156 AN: 110673 Hom.: 11204 Cov.: 23 AF XY: 0.484 AC XY: 15956 AN XY: 32957

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.521

Alfa AF: 0.599 Hom.: 19092

Bravo AF: 0.448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs498177; hg19: chrX-113824690;