Variant 7-7969475-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138426.4(GLCCI1):c.125G>C(p.Gly42Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000327 in 916,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G42S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

GLCCI1
NM_138426.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

GLCCI1 (HGNC:18713): (glucocorticoid induced 1) This gene encodes a protein of unknown function. Expression of this gene is induced by glucocorticoids and may be an early marker for glucocorticoid-induced apoptosis. Single nucleotide polymorphisms in this gene are associated with a decreased response to inhaled glucocorticoids in asthmatic patients. [provided by RefSeq, Feb 2012]

GLCCI1 links:

GLCCI1-DT (HGNC:40852): (GLCCI1 divergent transcript)

GLCCI1-DT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.116814494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLCCI1	NM_138426.4 linkuse as main transcript	c.125G>C	p.Gly42Ala	missense_variant	1/8	ENST00000223145.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLCCI1	ENST00000223145.10 linkuse as main transcript	c.125G>C	p.Gly42Ala	missense_variant	1/8	1	NM_138426.4	P1
GLCCI1-DT	ENST00000428660.1 linkuse as main transcript	n.132+297C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000327

AC:

AN:

916176

Hom.:

Cov.:

AF XY:

0.00000465

AC XY:

AN XY:

430106

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000367

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.125G>C (p.G42A) alteration is located in exon 1 (coding exon 1) of the GLCCI1 gene. This alteration results from a G to C substitution at nucleotide position 125, causing the glycine (G) at amino acid position 42 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.014

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.69

REVEL

Benign

0.25

Sift

Benign

0.094

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.21

MutPred

0.12

Loss of relative solvent accessibility (P = 0.0071);

MVP

0.29

MPC

0.91

ClinPred

0.32

GERP RS

0.78

Varity_R

0.077

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over