Genetic Variant GMEB2:c.*193T>C (chr20-63589896-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012384.5(GMEB2):c.*193T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 431,982 control chromosomes in the GnomAD database, including 65,439 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 21385 hom., cov: 34)

Exomes 𝑓: 0.54 ( 44054 hom. )

Consequence

GMEB2
NM_012384.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.506

Publications

27 publications found

Variant links:

Genes affected

GMEB2 (HGNC:4371): (glucocorticoid modulatory element binding protein 2) This gene is a member of KDWK gene family. The product of this gene associates with GMEB1 protein, and the complex is essential for parvovirus DNA replication. Study of rat homolog implicates the role of this gene in modulation of transactivation by the glucocorticoid receptor bound to glucocorticoid response elements. This gene appears to use multiple polyadenylation sites. [provided by RefSeq, Jul 2008]

GMEB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMEB2	NM_012384.5 link	c.*193T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000370077.2	NP_036516.1	Q9UKD1B4DQS0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GMEB2	ENST00000370077.2 link	c.*193T>C	3_prime_UTR_variant	Exon 10 of 10	1	NM_012384.5	ENSP00000359094.1	Q9UKD1
GMEB2	ENST00000266068.5 link	c.*193T>C	3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000266068.1	Q9UKD1
GMEB2	ENST00000370069.5 link	c.*193T>C	3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000359086.1	Q5JTV1

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79026

AN:

152016

Hom.:

21386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.569

Gnomad AMR

AF:

0.538

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.508

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.552

GnomAD4 exome

AF:

0.545

AC:

152473

AN:

279848

Hom.:

44054

Cov.:

AF XY:

0.546

AC XY:

78306

AN XY:

143348

show subpopulations

African (AFR)

AF:

0.428

AC:

3303

AN:

7720

American (AMR)

AF:

0.515

AC:

4614

AN:

8954

Ashkenazi Jewish (ASJ)

AF:

0.668

AC:

6517

AN:

9760

East Asian (EAS)

AF:

0.193

AC:

4571

AN:

23744

South Asian (SAS)

AF:

0.351

AC:

3065

AN:

8742

European-Finnish (FIN)

AF:

0.524

AC:

12039

AN:

22954

Middle Eastern (MID)

AF:

0.618

AC:

854

AN:

1382

European-Non Finnish (NFE)

AF:

0.603

AC:

107743

AN:

178696

Other (OTH)

AF:

0.546

AC:

9767

AN:

17896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3452

6904

10355

13807

17259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.520

AC:

79050

AN:

152134

Hom.:

21385

Cov.:

AF XY:

0.512

AC XY:

38055

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.429

AC:

17803

AN:

41506

American (AMR)

AF:

0.538

AC:

8224

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.678

AC:

2350

AN:

3468

East Asian (EAS)

AF:

0.198

AC:

1026

AN:

5172

South Asian (SAS)

AF:

0.340

AC:

1641

AN:

4824

European-Finnish (FIN)

AF:

0.508

AC:

5375

AN:

10590

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.600

AC:

40763

AN:

67960

Other (OTH)

AF:

0.546

AC:

1155

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1982

3964

5947

7929

9911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.575

Hom.:

109572

Bravo

AF:

0.518

Asia WGS

AF:

0.279

AC:

970

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.8

(source)

DANN

Benign

0.40

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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20-63589896-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over