rs2428707

Positions:

• chrX-114765807-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000868.4(HTR2C):​c.349+34200T>C 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 0.76 (23507 hom., 24894 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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]

LOC105373313 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2C	NM_000868.4	c.349+34200T>C		intron_variant		ENST00000276198.6
LOC105373313	XR_001755943.2	n.573+23536A>G		intron_variant, non_coding_transcript_variant
HTR2C	NM_001256760.3	c.349+34200T>C		intron_variant
HTR2C	NM_001256761.3	c.349+34200T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2C	ENST00000276198.6	c.349+34200T>C		intron_variant		1	NM_000868.4	P1
HTR2C	ENST00000371950.3	c.349+34200T>C		intron_variant		1
HTR2C	ENST00000371951.5	c.349+34200T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 84140 AN: 109943 Hom.: 23519 Cov.: 22 AF XY: 0.772 AC XY: 24878 AN XY: 32211

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.821

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: 0.765 AC: 84136 AN: 109990 Hom.: 23507 Cov.: 22 AF XY: 0.771 AC XY: 24894 AN XY: 32268

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.821

Alfa AF: 0.809 Hom.: 11978

Bravo AF: 0.756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2428707; hg19: chrX-114000359;