chr7-7969361-C-A

Variant names:

• chr7-7969361-C-A
• rs771224097
• NM_138426.4:c.11C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138426.4(GLCCI1):​c.11C>A​(p.Ala4Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000666 in 150,132 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. A4V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLCCI1 NM_138426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17160058).

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.11C>A	p.Ala4Asp	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.11C>A	p.Ala4Asp	missense	Exon 1 of 8	ENSP00000223145.5	Q86VQ1
	GLCCI1	ENST00000865612.1		c.11C>A	p.Ala4Asp	missense	Exon 1 of 8	ENSP00000535671.1
	GLCCI1	ENST00000924964.1		c.11C>A	p.Ala4Asp	missense	Exon 1 of 8	ENSP00000595023.1

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150132 Hom.: 0 Cov.: 30

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1187030 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 586956

African (AFR) AF: 0.00 AC: 0 AN: 24626

American (AMR) AF: 0.00 AC: 0 AN: 27546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18942

East Asian (EAS) AF: 0.00 AC: 0 AN: 25090

South Asian (SAS) AF: 0.00 AC: 0 AN: 63872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3970

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 949872

Other (OTH) AF: 0.00 AC: 0 AN: 47070

GnomAD4 genome AF: 0.00000666 AC: 1 AN: 150132 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73222

African (AFR) AF: 0.00 AC: 0 AN: 40856

American (AMR) AF: 0.00 AC: 0 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67372

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.65
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		0.94	P
Vest4		0.15
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.43
MPC		1.0
ClinPred		0.71	D
PromoterAI		-0.024	Neutral
Varity_R		0.51
gMVP		0.42
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

dbSNP: rs771224097; hg19: chr7-8008992;