Genetic Variant HTR2C:c.-697C>G (chrX-114584109-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_000868.4(HTR2C):c.-697C>G variant causes a 5 prime UTR 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 0.66 ( 17035 hom., 21550 hem., cov: 23)

Exomes 𝑓: 0.73 ( 52 hom. 100 hem. )

Failed GnomAD Quality Control

Consequence

HTR2C
NM_000868.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.377

Publications

86 publications found

Variant links:

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]

HTR2C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4 link	c.-697C>G	5_prime_UTR_variant	Exon 1 of 6	ENST00000276198.6	NP_000859.2	P28335-1
HTR2C	NM_001256760.3 link	c.-788C>G	5_prime_UTR_variant	Exon 1 of 7		NP_001243689.2	P28335-1
HTR2C	NM_001256761.3 link	c.-697C>G	5_prime_UTR_variant	Exon 1 of 6		NP_001243690.2	P28335-2K9J958

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTR2C	ENST00000276198.6 link	c.-697C>G	5_prime_UTR_variant	Exon 1 of 6	1	NM_000868.4	ENSP00000276198.1	P28335-1
HTR2C	ENST00000371951.5 link	c.-788C>G	5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000361019.1	P28335-1
HTR2C	ENST00000371950.3 link	c.-697C>G	5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

72811

AN:

110478

Hom.:

17046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.791

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.847

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.660

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.691

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.729

AC:

239

AN:

328

Hom.:

Cov.:

AF XY:

0.735

AC XY:

100

AN XY:

136

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.743

AC:

208

AN:

280

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.595

AC:

AN:

Other (OTH)

AF:

0.778

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.659

AC:

72813

AN:

110529

Hom.:

17035

Cov.:

AF XY:

0.657

AC XY:

21550

AN XY:

32779

show subpopulations

African (AFR)

AF:

0.631

AC:

19199

AN:

30438

American (AMR)

AF:

0.654

AC:

6871

AN:

10505

Ashkenazi Jewish (ASJ)

AF:

0.634

AC:

1667

AN:

2628

East Asian (EAS)

AF:

0.847

AC:

2896

AN:

3420

South Asian (SAS)

AF:

0.601

AC:

1559

AN:

2596

European-Finnish (FIN)

AF:

0.724

AC:

4209

AN:

5815

Middle Eastern (MID)

AF:

0.634

AC:

135

AN:

213

European-Non Finnish (NFE)

AF:

0.658

AC:

34703

AN:

52734

Other (OTH)

AF:

0.692

AC:

1045

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

884

1769

2653

3538

4422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.477

Hom.:

1983

Bravo

AF:

0.654

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.5

(source)

PhyloP100

-0.38

PromoterAI

-0.0026

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over