Genetic Variant GCHFR:c.36+26G>C (chr15-40764242-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005258.3(GCHFR):c.36+26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GCHFR
NM_005258.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.379

Publications

5 publications found

Variant links:

Genes affected

GCHFR (HGNC:4194): (GTP cyclohydrolase I feedback regulator) GTP cyclohydrolase I feedback regulatory protein binds to and mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase I. The regulatory protein, GCHFR, consists of a homodimer. It is postulated that GCHFR may play a role in regulating phenylalanine metabolism in the liver and in the production of biogenic amine neurotransmitters and nitric oxide. [provided by RefSeq, Jul 2008]

GCHFR links:

ENSG00000310466 (HGNC:):

ENSG00000310466 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCHFR	NM_005258.3 link	c.36+26G>C		intron_variant	Intron 1 of 2	ENST00000260447.6	NP_005249.1	P30047-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCHFR	ENST00000260447.6 link	c.36+26G>C		intron_variant	Intron 1 of 2	1	NM_005258.3	ENSP00000260447.4		P30047-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1393536

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687620

African (AFR)

AF:

0.00

AC:

AN:

30662

American (AMR)

AF:

0.00

AC:

AN:

35778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24764

East Asian (EAS)

AF:

0.00

AC:

AN:

35410

South Asian (SAS)

AF:

0.00

AC:

AN:

78696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077284

Other (OTH)

AF:

0.00

AC:

AN:

57688

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.0

(source)

DANN

Benign

0.60

PhyloP100

-0.38

PromoterAI

-0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over