Variant 7-7969373-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138426.4(GLCCI1):c.23C>G(p.Ser8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 1,339,064 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

GLCCI1
NM_138426.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

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:):

GLCCI1-DT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04730919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLCCI1	NM_138426.4 linkuse as main transcript	c.23C>G	p.Ser8Cys	missense_variant	1/8	ENST00000223145.10	NP_612435.1	Q86VQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLCCI1	ENST00000223145.10 linkuse as main transcript	c.23C>G	p.Ser8Cys	missense_variant	1/8	1	NM_138426.4	ENSP00000223145.5	Q86VQ1
GLCCI1-DT	ENST00000428660.1 linkuse as main transcript	n.132+399G>C		intron_variant		4
ENSG00000283549	ENST00000469183.5 linkuse as main transcript	n.492-34535C>G		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000303

AC:

AN:

132150

Hom.:

AF XY:

0.0000133

AC XY:

AN XY:

75428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000550

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000299

AC:

AN:

1339064

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

665076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000131

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000277

AC:

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

Sep 10, 2024

The c.23C>G (p.S8C) alteration is located in exon 1 (coding exon 1) of the GLCCI1 gene. This alteration results from a C to G substitution at nucleotide position 23, causing the serine (S) at amino acid position 8 to be replaced by a cysteine (C). 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

0.089

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.010

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.39

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.15

REVEL

Benign

0.044

Sift

Uncertain

0.015

Sift4G

Benign

0.081

Polyphen

0.0030

Vest4

0.23

MutPred

0.29

Loss of phosphorylation at S8 (P = 4e-04);

MVP

0.27

MPC

0.81

ClinPred

0.22

GERP RS

1.5

Varity_R

0.090

gMVP

0.27

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.

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