rs1414334

Positions:

• chrX-114903581-C-G

Variant summary

Our verdict is Likely benign. Variant got -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

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 -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 id is 225952.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-114903581-C-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.551-3008C>G		intron_variant		ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.551-3008C>G		intron_variant			NP_001243689.2
HTR2C	NM_001256761.3	c.456-3008C>G		intron_variant			NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.551-3008C>G		intron_variant		1	NM_000868.4	ENSP00000276198	P1
HTR2C	ENST00000371950.3	c.456-3008C>G		intron_variant		1		ENSP00000361018
HTR2C	ENST00000371951.5	c.551-3008C>G		intron_variant		1		ENSP00000361019	P1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 86188 AN: 111142 Hom.: 23880 Cov.: 24 AF XY: 0.787 AC XY: 26229 AN XY: 33346

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

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.893

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.822

Alfa AF: 0.809 Hom.: 6884

Bravo AF: 0.766

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.69
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs1414334; hg19: chrX-114138144;