rs2878169

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000161.3(GCH1):​c.509+406C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 242,470 control chromosomes in the GnomAD database, including 1,126 homozygotes. 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 0.073 ( 640 hom., cov: 32)
Exomes 𝑓: 0.083 ( 486 hom. )

Consequence

GCH1
NM_000161.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.249
Variant links:
Genes affected
GCH1 (HGNC:4193): (GTP cyclohydrolase 1) This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. [provided by RefSeq, Jul 2008]
RNU6ATAC9P (HGNC:46908): (RNA, U6atac small nuclear 9, pseudogene)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GCH1NM_000161.3 linkuse as main transcriptc.509+406C>A intron_variant ENST00000491895.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GCH1ENST00000491895.7 linkuse as main transcriptc.509+406C>A intron_variant 1 NM_000161.3 P1P30793-1
RNU6ATAC9PENST00000516210.1 linkuse as main transcriptn.61G>T non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0730
AC:
11097
AN:
152114
Hom.:
640
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0164
Gnomad AMI
AF:
0.152
Gnomad AMR
AF:
0.0504
Gnomad ASJ
AF:
0.0418
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.0180
Gnomad FIN
AF:
0.166
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.109
Gnomad OTH
AF:
0.0602
GnomAD4 exome
AF:
0.0835
AC:
7534
AN:
90240
Hom.:
486
Cov.:
0
AF XY:
0.0799
AC XY:
3772
AN XY:
47216
show subpopulations
Gnomad4 AFR exome
AF:
0.0132
Gnomad4 AMR exome
AF:
0.0431
Gnomad4 ASJ exome
AF:
0.0491
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0197
Gnomad4 FIN exome
AF:
0.142
Gnomad4 NFE exome
AF:
0.111
Gnomad4 OTH exome
AF:
0.0894
GnomAD4 genome
AF:
0.0729
AC:
11096
AN:
152230
Hom.:
640
Cov.:
32
AF XY:
0.0740
AC XY:
5505
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0163
Gnomad4 AMR
AF:
0.0503
Gnomad4 ASJ
AF:
0.0418
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.0180
Gnomad4 FIN
AF:
0.166
Gnomad4 NFE
AF:
0.109
Gnomad4 OTH
AF:
0.0596
Alfa
AF:
0.111
Hom.:
167
Bravo
AF:
0.0603
Asia WGS
AF:
0.0130
AC:
46
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
3.6
DANN
Benign
0.51

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2878169; hg19: chr14-55325993; API