rs1801412

Variant names:

• chrX-114908141-T-G
• rs1801412
• NM_000868.4:c.*726T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000868.4(HTR2C):​c.*726T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 112,298 control chromosomes in the GnomAD database, including 86 homozygotes. There are 1,337 hemizygotes in GnomAD. 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 0.040 (86 hom., 1337 hem., cov: 23)
  • Exomes 𝑓: 0.010 (0 hom. 0 hem.)
• Consequence: HTR2C NM_000868.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.*726T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.*726T>G		3_prime_UTR_variant	Exon 7 of 7		NP_001243689.2
HTR2C	NM_001256761.3	c.*1261T>G		3_prime_UTR_variant	Exon 6 of 6		NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.*726T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.*726T>G		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.*1261T>G		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 4438 AN: 111946 Hom.: 86 Cov.: 23 AF XY: 0.0392 AC XY: 1339 AN XY: 34122

Gnomad AFR AF: 0.00831

Gnomad AMI AF: 0.0174

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.0393

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0483

GnomAD4 exome AF: 0.0100 AC: 3 AN: 299 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 129

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0396 AC: 4436 AN: 111999 Hom.: 86 Cov.: 23 AF XY: 0.0391 AC XY: 1337 AN XY: 34185

Gnomad4 AFR AF: 0.00830

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.0933

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.0514

Gnomad4 OTH AF: 0.0490

Alfa AF: 0.0518 Hom.: 2153

Bravo AF: 0.0396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.81

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: rs1801412; hg19: chrX-114142704;