rs12838742

Positions:

• chrX-114618753-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000868.4(HTR2C):​c.-80+4872C>T 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 0.66 (17262 hom., 21248 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-80+4872C>T		intron_variant		ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-171+4872C>T		intron_variant			NP_001243689.2
HTR2C	NM_001256761.3	c.-80+4872C>T		intron_variant			NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-80+4872C>T		intron_variant		1	NM_000868.4	ENSP00000276198	P1
HTR2C	ENST00000371950.3	c.-80+4872C>T		intron_variant		1		ENSP00000361018
HTR2C	ENST00000371951.5	c.-171+4872C>T		intron_variant		1		ENSP00000361019	P1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 72815 AN: 109861 Hom.: 17270 Cov.: 22 AF XY: 0.661 AC XY: 21228 AN XY: 32137

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.706

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: 0.663 AC: 72826 AN: 109910 Hom.: 17262 Cov.: 22 AF XY: 0.660 AC XY: 21248 AN XY: 32194

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.706

Alfa AF: 0.664 Hom.: 7731

Bravo AF: 0.669

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12838742; hg19: chrX-113853211;