Genetic Variant NM_017769.5:c.238-20A>G (chr14-30592303-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_017769.5(G2E3):c.238-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,608,702 control chromosomes in the GnomAD database, including 2,233 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 0.033 ( 282 hom., cov: 32)

Exomes 𝑓: 0.023 ( 1951 hom. )

Consequence

G2E3
NM_017769.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.64

Publications

4 publications found

Variant links:

Genes affected

G2E3 (HGNC:20338): (G2/M-phase specific E3 ubiquitin protein ligase) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in apoptotic process and protein ubiquitination. Predicted to act upstream of or within blastocyst development; negative regulation of intrinsic apoptotic signaling pathway; and protein polyubiquitination. Located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

G2E3 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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G2E3	NM_017769.5 link	c.238-20A>G		intron_variant	Intron 4 of 14	ENST00000206595.11	NP_060239.2	Q7L622

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G2E3	ENST00000206595.11 link	c.238-20A>G		intron_variant	Intron 4 of 14	1	NM_017769.5	ENSP00000206595.6		Q7L622

Frequencies

GnomAD3 genomes

AF:

0.0332

AC:

5037

AN:

151916

Hom.:

275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.0560

Gnomad SAS

AF:

0.0183

Gnomad FIN

AF:

0.00633

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.0447

GnomAD2 exomes

AF:

0.0535

AC:

13367

AN:

249954

AF XY:

0.0446

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.0155

Gnomad EAS exome

AF:

0.0448

Gnomad FIN exome

AF:

0.00700

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0425

GnomAD4 exome

AF:

0.0232

AC:

33861

AN:

1456668

Hom.:

1951

Cov.:

AF XY:

0.0221

AC XY:

16049

AN XY:

724948

show subpopulations

African (AFR)

AF:

0.0213

AC:

710

AN:

33304

American (AMR)

AF:

0.259

AC:

11543

AN:

44488

Ashkenazi Jewish (ASJ)

AF:

0.0166

AC:

433

AN:

26076

East Asian (EAS)

AF:

0.0526

AC:

2079

AN:

39542

South Asian (SAS)

AF:

0.0208

AC:

1787

AN:

86080

European-Finnish (FIN)

AF:

0.00755

AC:

403

AN:

53348

Middle Eastern (MID)

AF:

0.0167

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0139

AC:

15423

AN:

1107890

Other (OTH)

AF:

0.0230

AC:

1387

AN:

60184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1268

2536

3804

5072

6340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

744

1488

2232

2976

3720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0333

AC:

5056

AN:

152034

Hom.:

282

Cov.:

AF XY:

0.0355

AC XY:

2639

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0239

AC:

993

AN:

41468

American (AMR)

AF:

0.161

AC:

2455

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3468

East Asian (EAS)

AF:

0.0559

AC:

289

AN:

5170

South Asian (SAS)

AF:

0.0185

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00633

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0148

AC:

1007

AN:

67964

Other (OTH)

AF:

0.0437

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

227

454

681

908

1135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0279

Hom.:

123

Bravo

AF:

0.0474

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0020

(source)

DANN

Benign

0.51

PhyloP100

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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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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