Variant 14-54842552-A-AAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000161.3(GCH1):c.*1464_*1465insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 153,894 control chromosomes in the GnomAD database, including 38 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.016 ( 37 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1 hom. )

Consequence

GCH1
NM_000161.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0760

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]

GCH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 14-54842552-A-AAT is Benign according to our data. Variant chr14-54842552-A-AAT is described in ClinVar as [Likely_benign]. Clinvar id is 313364.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0163 (2483/152272) while in subpopulation SAS AF= 0.0482 (232/4814). AF 95% confidence interval is 0.0431. There are 37 homozygotes in gnomad4. There are 1342 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCH1	NM_000161.3 linkuse as main transcript	c.1464_1465insAT		3_prime_UTR_variant	6/6	ENST00000491895.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCH1	ENST00000491895.7 linkuse as main transcript	c.1464_1465insAT		3_prime_UTR_variant	6/6	1	NM_000161.3	P1	P30793-1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2485

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.00924

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0486

Gnomad FIN

AF:

0.0472

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0187

Gnomad OTH

AF:

0.0182

GnomAD4 exome

AF:

0.0154

AC:

AN:

1622

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

AN XY:

886

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0417

Gnomad4 FIN exome

AF:

0.0282

Gnomad4 NFE exome

AF:

0.0142

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.0163

AC:

2483

AN:

152272

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1342

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.0159

Gnomad4 ASJ

AF:

0.00924

Gnomad4 EAS

AF:

0.00250

Gnomad4 SAS

AF:

0.0482

Gnomad4 FIN

AF:

0.0472

Gnomad4 NFE

AF:

0.0187

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GTP cyclohydrolase I deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Dopa-responsive dystonia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over