chr7-7969630-A-C

Variant names:

• chr7-7969630-A-C
• NM_138426.4:c.280A>C
• GLCCI1 p.Ser94Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138426.4(GLCCI1):​c.280A>C​(p.Ser94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GLCCI1 NM_138426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 0 publications found

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

ENSG00000283549 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26551893).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLCCI1	NM_138426.4	MANE Select	c.280A>C	p.Ser94Arg	missense	Exon 1 of 8	NP_612435.1	Q86VQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLCCI1	ENST00000223145.10	TSL:1 MANE Select	c.280A>C	p.Ser94Arg	missense	Exon 1 of 8	ENSP00000223145.5	Q86VQ1
	GLCCI1	ENST00000865612.1		c.280A>C	p.Ser94Arg	missense	Exon 1 of 8	ENSP00000535671.1
	GLCCI1	ENST00000924964.1		c.280A>C	p.Ser94Arg	missense	Exon 1 of 8	ENSP00000595023.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.044
Eigen_PC	Benign	-0.084
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.39	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.089
Sift	Benign	0.087	T
Sift4G	Benign	0.087	T
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.36
Mutation Taster		=59/41	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-8009261;