rs1023574

Variant names:

• chrX-114620562-C-G
• rs1023574
• NM_000868.4:c.-80+6681C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-114620562-C-G
• chrX-114620562-C-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+6681C>G 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 (17255 hom., 21202 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 7 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=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000868.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	NM_000868.4	MANE Select	c.-80+6681C>G		intron	N/A	NP_000859.2	P28335-1
	HTR2C	NM_001256760.3		c.-171+6681C>G		intron	N/A	NP_001243689.2	P28335-1
	HTR2C	NM_001256761.3		c.-80+6681C>G		intron	N/A	NP_001243690.2	P28335-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	ENST00000276198.6	TSL:1 MANE Select	c.-80+6681C>G		intron	N/A	ENSP00000276198.1	P28335-1
	HTR2C	ENST00000371951.5	TSL:1	c.-171+6681C>G		intron	N/A	ENSP00000361019.1	P28335-1
	HTR2C	ENST00000371950.3	TSL:1	c.-80+6681C>G		intron	N/A	ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes AF: 0.664 AC: 72756 AN: 109625 Hom.: 17263 Cov.: 22

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.667

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.709

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: 0.664 AC: 72767 AN: 109671 Hom.: 17255 Cov.: 22 AF XY: 0.663 AC XY: 21202 AN XY: 32001

African (AFR) AF: 0.619 AC: 18660 AN: 30160

American (AMR) AF: 0.741 AC: 7533 AN: 10165

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 1679 AN: 2633

East Asian (EAS) AF: 0.852 AC: 2949 AN: 3462

South Asian (SAS) AF: 0.551 AC: 1434 AN: 2603

European-Finnish (FIN) AF: 0.726 AC: 4084 AN: 5627

Middle Eastern (MID) AF: 0.645 AC: 136 AN: 211

European-Non Finnish (NFE) AF: 0.659 AC: 34699 AN: 52638

Other (OTH) AF: 0.709 AC: 1061 AN: 1497

Alfa AF: 0.657 Hom.: 4926

Bravo AF: 0.669

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs1023574; hg19: chrX-113855020;