rs11167435

Variant names:

• chrX-114708007-A-T
• rs11167435
• NM_000868.4:c.-79-18851A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000868.4(HTR2C):​c.-79-18851A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 111,045 control chromosomes in the GnomAD database, including 619 homozygotes. There are 3,248 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 0.10 (619 hom., 3248 hem., cov: 23)
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-79-18851A>T		intron_variant	Intron 2 of 5	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-170-9579A>T		intron_variant	Intron 2 of 6		NP_001243689.2
HTR2C	NM_001256761.3	c.-79-18851A>T		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.-79-18851A>T		intron_variant	Intron 2 of 5	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.-170-9579A>T		intron_variant	Intron 2 of 6	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.-79-18851A>T		intron_variant	Intron 2 of 5	1		ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 11642 AN: 111008 Hom.: 618 Cov.: 23

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.0946

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 11644 AN: 111045 Hom.: 619 Cov.: 23 AF XY: 0.0976 AC XY: 3248 AN XY: 33271

African (AFR) AF: 0.0225 AC: 693 AN: 30788

American (AMR) AF: 0.0604 AC: 625 AN: 10344

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 566 AN: 2640

East Asian (EAS) AF: 0.0120 AC: 42 AN: 3510

South Asian (SAS) AF: 0.0964 AC: 255 AN: 2646

European-Finnish (FIN) AF: 0.109 AC: 641 AN: 5866

Middle Eastern (MID) AF: 0.221 AC: 46 AN: 208

European-Non Finnish (NFE) AF: 0.161 AC: 8510 AN: 52857

Other (OTH) AF: 0.0954 AC: 144 AN: 1510

Alfa AF: 0.117 Hom.: 625

Bravo AF: 0.0975

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11167435; hg19: chrX-113942422;