Genetic Variant GLCCI1:p.Ser5Thr (chr7-7969363-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138426.4(GLCCI1):c.13T>A(p.Ser5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000853 in 1,171,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S5A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

GLCCI1
NM_138426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.633

Publications

0 publications found

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:

ENSG00000283549 (HGNC:):

ENSG00000283549 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08579263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLCCI1	NM_138426.4 link	c.13T>A	p.Ser5Thr	missense_variant	Exon 1 of 8	ENST00000223145.10	NP_612435.1	Q86VQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLCCI1	ENST00000223145.10 link	c.13T>A	p.Ser5Thr	missense_variant	Exon 1 of 8	1	NM_138426.4	ENSP00000223145.5	Q86VQ1
GLCCI1-DT	ENST00000428660.1 link	n.132+409A>T		intron_variant	Intron 1 of 1	4
ENSG00000283549	ENST00000469183.5 link	n.492-34545T>A		intron_variant	Intron 4 of 4	5
GLCCI1-DT	ENST00000837755.1 link	n.130+409A>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.53e-7

AC:

AN:

1171660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

579276

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

24192

American (AMR)

AF:

0.00

AC:

AN:

27194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18398

East Asian (EAS)

AF:

0.00

AC:

AN:

24238

South Asian (SAS)

AF:

0.00

AC:

AN:

63380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3894

European-Non Finnish (NFE)

AF:

0.00000106

AC:

AN:

939016

Other (OTH)

AF:

0.00

AC:

AN:

46208

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.012

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.29

M_CAP

Benign

0.0017

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.81

PhyloP100

-0.63

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.19

REVEL

Benign

0.043

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.025

Polyphen

0.22

Vest4

0.18

MutPred

0.18

Gain of relative solvent accessibility (P = 0.0479);

MVP

0.29

MPC

0.40

ClinPred

0.31

PromoterAI

-0.0048

Neutral

(source)

Varity_R

0.46

gMVP

0.18

Mutation Taster

=96/4

polymorphism

(source)

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