dbSNP rs776980379: 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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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