NM_000868.4:c.-80+21906A>C

Variant names:

• chrX-114635787-A-C
• rs17095676
• NM_000868.4:c.-80+21906A>C

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+21906A>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 0.85 (27889 hom., 28109 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628
• Publications: 1 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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-80+21906A>C		intron_variant	Intron 2 of 5	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-171+21906A>C		intron_variant	Intron 2 of 6		NP_001243689.2
HTR2C	NM_001256761.3	c.-80+21906A>C		intron_variant	Intron 2 of 5		NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-80+21906A>C		intron_variant	Intron 2 of 5	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.-171+21906A>C		intron_variant	Intron 2 of 6	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.-80+21906A>C		intron_variant	Intron 2 of 5	1		ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.848 AC: 93840 AN: 110718 Hom.: 27895 Cov.: 23

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.786

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.873

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: 0.848 AC: 93886 AN: 110771 Hom.: 27889 Cov.: 23 AF XY: 0.852 AC XY: 28109 AN XY: 32979

African (AFR) AF: 0.824 AC: 25110 AN: 30473

American (AMR) AF: 0.919 AC: 9497 AN: 10339

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2066 AN: 2637

East Asian (EAS) AF: 0.988 AC: 3476 AN: 3518

South Asian (SAS) AF: 0.878 AC: 2303 AN: 2624

European-Finnish (FIN) AF: 0.884 AC: 5142 AN: 5819

Middle Eastern (MID) AF: 0.759 AC: 164 AN: 216

European-Non Finnish (NFE) AF: 0.836 AC: 44250 AN: 52954

Other (OTH) AF: 0.873 AC: 1321 AN: 1514

Alfa AF: 0.850 Hom.: 7358

Bravo AF: 0.849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
PhyloP100		-0.63

Splicing

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

Other links and lift over

dbSNP: rs17095676; hg19: chrX-113870258;