rs1414334

Variant names:

• chrX-114903581-C-G
• rs1414334
• NM_000868.4:c.551-3008C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-114903581-C-G
• chrX-114903581-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000868.4(HTR2C):​c.551-3008C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (23868 hom., 26246 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280
• Publications: 62 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-114903581-C-G is Benign according to our data. Variant chrX-114903581-C-G is described in ClinVar as Benign. ClinVar VariationId is 225952.Status of the report is criteria_provided_single_submitter, 1 stars.

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.551-3008C>G		intron	N/A	NP_000859.2	P28335-1
	HTR2C	NM_001256760.3		c.551-3008C>G		intron	N/A	NP_001243689.2	P28335-1
	HTR2C	NM_001256761.3		c.456-3008C>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.551-3008C>G		intron	N/A	ENSP00000276198.1	P28335-1
	HTR2C	ENST00000371951.5	TSL:1	c.551-3008C>G		intron	N/A	ENSP00000361019.1	P28335-1
	HTR2C	ENST00000371950.3	TSL:1	c.456-3008C>G		intron	N/A	ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes AF: 0.775 AC: 86188 AN: 111142 Hom.: 23880 Cov.: 24

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.824

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.822

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: 0.775 AC: 86185 AN: 111195 Hom.: 23868 Cov.: 24 AF XY: 0.786 AC XY: 26246 AN XY: 33409

African (AFR) AF: 0.553 AC: 16907 AN: 30566

American (AMR) AF: 0.889 AC: 9303 AN: 10463

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2151 AN: 2640

East Asian (EAS) AF: 0.991 AC: 3472 AN: 3505

South Asian (SAS) AF: 0.893 AC: 2385 AN: 2670

European-Finnish (FIN) AF: 0.887 AC: 5239 AN: 5909

Middle Eastern (MID) AF: 0.797 AC: 169 AN: 212

European-Non Finnish (NFE) AF: 0.844 AC: 44759 AN: 53034

Other (OTH) AF: 0.822 AC: 1244 AN: 1513

Alfa AF: 0.809 Hom.: 6884

Bravo AF: 0.766

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.69
DANN	Benign	0.84
PhyloP100		0.028
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1414334; hg19: chrX-114138144;