rs2428712

Variant names:

• chrX-114753044-A-G
• rs2428712
• NM_000868.4:c.349+21437A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000868.4(HTR2C):​c.349+21437A>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 0.78 (24447 hom., 24167 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 2 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]

ENSG00000306059 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.349+21437A>G		intron_variant	Intron 4 of 5	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.349+21437A>G		intron_variant	Intron 5 of 6		NP_001243689.2
HTR2C	NM_001256761.3	c.349+21437A>G		intron_variant	Intron 4 of 5		NP_001243690.2
LOC105373313	XR_001755943.2	n.574-22268T>C		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.349+21437A>G		intron_variant	Intron 4 of 5	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.349+21437A>G		intron_variant	Intron 5 of 6	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.349+21437A>G		intron_variant	Intron 4 of 5	1		ENSP00000361018.3
ENSG00000306059	ENST00000814999.1	n.406-22268T>C		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.785 AC: 85055 AN: 108366 Hom.: 24460 Cov.: 21

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.830

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: 0.785 AC: 85055 AN: 108403 Hom.: 24447 Cov.: 21 AF XY: 0.786 AC XY: 24167 AN XY: 30743

African (AFR) AF: 0.592 AC: 17690 AN: 29869

American (AMR) AF: 0.892 AC: 8927 AN: 10012

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2120 AN: 2607

East Asian (EAS) AF: 0.989 AC: 3370 AN: 3407

South Asian (SAS) AF: 0.887 AC: 2180 AN: 2457

European-Finnish (FIN) AF: 0.874 AC: 4621 AN: 5286

Middle Eastern (MID) AF: 0.784 AC: 163 AN: 208

European-Non Finnish (NFE) AF: 0.844 AC: 44218 AN: 52417

Other (OTH) AF: 0.830 AC: 1224 AN: 1475

Alfa AF: 0.824 Hom.: 10331

Bravo AF: 0.779

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
PhyloP100		-0.31

Splicing

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

Other links and lift over

dbSNP: rs2428712; hg19: chrX-113987484;