rs12847225

chrX-114669923-C-AchrX-114669923-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000868.4(HTR2C):c.-80+56042C>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 0.65 (16535 hom., 21136 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BS2: High Homozygotes in GnomAd at 16543 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2C	NM_000868.4	c.-80+56042C>A		intron_variant		ENST00000276198.6
HTR2C	NM_001256760.3	c.-170-47663C>A		intron_variant
HTR2C	NM_001256761.3	c.-80+56042C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2C	ENST00000276198.6	c.-80+56042C>A		intron_variant		1	NM_000868.4	P1
HTR2C	ENST00000371950.3	c.-80+56042C>A		intron_variant		1
HTR2C	ENST00000371951.5	c.-170-47663C>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 71536 AN: 110336 Hom.: 16543 Cov.: 23 AF XY: 0.648 AC XY: 21116 AN XY: 32604

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.701

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: 0.648 AC: 71542 AN: 110386 Hom.: 16535 Cov.: 23 AF XY: 0.647 AC XY: 21136 AN XY: 32664

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.701

Alfa AF: 0.584 Hom.: 5568

Bravo AF: 0.653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.080

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12847225; hg19: chrX-113904402;