Variant 7-7969361-C-T 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.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000718 in 1,337,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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: 𝑓 0.000027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

GLCCI1
NM_138426.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.654

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:

Genome browser will be placed here

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=0.12773517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLCCI1	NM_138426.4 linkuse as main transcript	c.11C>T	p.Ala4Val	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.11C>T	p.Ala4Val	missense_variant	1/8	1	NM_138426.4	ENSP00000223145.5	Q86VQ1
GLCCI1-DT	ENST00000428660.1 linkuse as main transcript	n.132+411G>A		intron_variant		4
ENSG00000283549	ENST00000469183.5 linkuse as main transcript	n.492-34547C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

150132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000594

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000345

AC:

AN:

115936

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000780

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000775

AC:

AN:

1187030

Hom.:

Cov.:

AF XY:

0.0000613

AC XY:

AN XY:

586956

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:

0.0000157

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000905

Gnomad4 OTH exome

AF:

0.000106

GnomAD4 genome

AF:

0.0000266

AC:

AN:

150132

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73222

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000594

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000929

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

Jun 26, 2024

The c.11C>T (p.A4V) alteration is located in exon 1 (coding exon 1) of the GLCCI1 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.48

M_CAP

Benign

0.0014

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.30

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.020

Polyphen

0.88

Vest4

0.089

MutPred

0.22

Gain of sheet (P = 0.0344);

MVP

0.27

MPC

0.69

ClinPred

0.36

Varity_R

0.25

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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