rs12838742

Variant names:

• chrX-114618753-C-T
• rs12838742
• NM_000868.4:c.-80+4872C>T

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 2 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 -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-80+4872C>T		intron_variant	Intron 2 of 5	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-171+4872C>T		intron_variant	Intron 2 of 6		NP_001243689.2
HTR2C	NM_001256761.3	c.-80+4872C>T		intron_variant	Intron 2 of 5		NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-80+4872C>T		intron_variant	Intron 2 of 5	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.-171+4872C>T		intron_variant	Intron 2 of 6	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.-80+4872C>T		intron_variant	Intron 2 of 5	1		ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.663 AC: 72815 AN: 109861 Hom.: 17270 Cov.: 22

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

African (AFR) AF: 0.616 AC: 18672 AN: 30290

American (AMR) AF: 0.743 AC: 7600 AN: 10226

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 1676 AN: 2629

East Asian (EAS) AF: 0.852 AC: 2947 AN: 3457

South Asian (SAS) AF: 0.546 AC: 1427 AN: 2613

European-Finnish (FIN) AF: 0.722 AC: 4136 AN: 5732

Middle Eastern (MID) AF: 0.639 AC: 133 AN: 208

European-Non Finnish (NFE) AF: 0.659 AC: 34647 AN: 52582

Other (OTH) AF: 0.706 AC: 1059 AN: 1499

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
PhyloP100		0.0020

Splicing

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

Other links and lift over

dbSNP: rs12838742; hg19: chrX-113853211;