chr7-7969503-C-G

Variant names:

• chr7-7969503-C-G
• NM_138426.4:c.153C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_138426.4(GLCCI1):​c.153C>G​(p.Cys51Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C51G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000050 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLCCI1 NM_138426.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.540
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21330553).

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.153C>G	p.Cys51Trp	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.153C>G	p.Cys51Trp	missense	Exon 1 of 8	ENSP00000223145.5	Q86VQ1
	GLCCI1	ENST00000865612.1		c.153C>G	p.Cys51Trp	missense	Exon 1 of 8	ENSP00000535671.1
	GLCCI1	ENST00000924964.1		c.153C>G	p.Cys51Trp	missense	Exon 1 of 8	ENSP00000595023.1

Frequencies

GnomAD3 genomes AF: 0.00000691 AC: 1 AN: 144822 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000208

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000497 AC: 4 AN: 804850 Hom.: 0 Cov.: 28 AF XY: 0.00000267 AC XY: 1 AN XY: 375036

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

African (AFR) AF: 0.00 AC: 0 AN: 15074

American (AMR) AF: 0.00 AC: 0 AN: 1722

Ashkenazi Jewish (ASJ) AF: 0.000186 AC: 1 AN: 5386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4288

South Asian (SAS) AF: 0.00 AC: 0 AN: 16456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1640

European-Non Finnish (NFE) AF: 0.00000274 AC: 2 AN: 730856

Other (OTH) AF: 0.0000371 AC: 1 AN: 26962

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00128442), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000690 AC: 1 AN: 144946 Hom.: 0 Cov.: 31 AF XY: 0.0000142 AC XY: 1 AN XY: 70564

African (AFR) AF: 0.00 AC: 0 AN: 40560

American (AMR) AF: 0.00 AC: 0 AN: 14624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.000209 AC: 1 AN: 4790

South Asian (SAS) AF: 0.00 AC: 0 AN: 4444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65520

Other (OTH) AF: 0.00 AC: 0 AN: 2030

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.54
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.012	D
Polyphen		0.86	P
Vest4		0.30
MutPred		0.26		Gain of MoRF binding (P = 0.0191)
MVP		0.23
MPC		1.0
ClinPred		0.76	D
GERP RS		1.8
PromoterAI		0.19	Neutral
Varity_R		0.28
gMVP		0.25
Mutation Taster		=76/24	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

Other links and lift over

hg19: chr7-8009134;