rs541216640

Variant names:

• chr7-7969480-G-A
• rs541216640
• NM_138426.4:c.130G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-7969480-G-A
• chr7-7969480-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_138426.4(GLCCI1):​c.130G>A​(p.Gly44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000345 in 1,005,110 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 30)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: GLCCI1 NM_138426.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025700659).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.130G>A	p.Gly44Ser	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.130G>A	p.Gly44Ser	missense	Exon 1 of 8	ENSP00000223145.5	Q86VQ1
	GLCCI1	ENST00000865612.1		c.130G>A	p.Gly44Ser	missense	Exon 1 of 8	ENSP00000535671.1
	GLCCI1	ENST00000924964.1		c.130G>A	p.Gly44Ser	missense	Exon 1 of 8	ENSP00000595023.1

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 226 AN: 138438 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00104

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: 0.0000306

Gnomad OTH AF: 0.00155

GnomAD2 exomes AF: 0.00 AC: 0 AN: 322 AF XY: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000133 AC: 115 AN: 866588 Hom.: 0 Cov.: 28 AF XY: 0.000121 AC XY: 49 AN XY: 404894

African (AFR) AF: 0.00563 AC: 92 AN: 16338

American (AMR) AF: 0.00 AC: 0 AN: 2244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6340

East Asian (EAS) AF: 0.00 AC: 0 AN: 6298

South Asian (SAS) AF: 0.00 AC: 0 AN: 17542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1820

European-Non Finnish (NFE) AF: 0.00000384 AC: 3 AN: 781776

Other (OTH) AF: 0.000679 AC: 20 AN: 29438

GnomAD4 genome AF: 0.00167 AC: 232 AN: 138522 Hom.: 2 Cov.: 30 AF XY: 0.00188 AC XY: 127 AN XY: 67594

African (AFR) AF: 0.00624 AC: 212 AN: 33984

American (AMR) AF: 0.00104 AC: 15 AN: 14486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3342

East Asian (EAS) AF: 0.00 AC: 0 AN: 4958

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000306 AC: 2 AN: 65346

Other (OTH) AF: 0.00154 AC: 3 AN: 1952

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00159

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	Benign	0.094
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.010	N
REVEL	Benign	0.067
Sift	Benign	0.60	T
Sift4G	Benign	1.0	T
Polyphen		0.99	D
Vest4		0.25
MVP		0.35
MPC		0.90
ClinPred		0.73	D
GERP RS		1.2
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.030
gMVP		0.21
Mutation Taster		=97/3	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

dbSNP: rs541216640; hg19: chr7-8009111;