chr14-30592303-A-G

Position:

• chr14-30592303-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000206595.11(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 ENST00000206595.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
G2E3	NM_017769.5	c.238-20A>G		intron_variant		ENST00000206595.11	NP_060239.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G2E3	ENST00000206595.11	c.238-20A>G		intron_variant		1	NM_017769.5	ENSP00000206595	P1

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 5037 AN: 151916 Hom.: 275 Cov.: 32

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

GnomAD3 exomes AF: 0.0535 AC: 13367 AN: 249954 Hom.: 1468 AF XY: 0.0446 AC XY: 6034 AN XY: 135164

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 SAS exome AF: 0.0202

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.: 28 AF XY: 0.0221 AC XY: 16049 AN XY: 724948

Gnomad4 AFR exome AF: 0.0213

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.0166

Gnomad4 EAS exome AF: 0.0526

Gnomad4 SAS exome AF: 0.0208

Gnomad4 FIN exome AF: 0.00755

Gnomad4 NFE exome AF: 0.0139

Gnomad4 OTH exome AF: 0.0230

GnomAD4 genome AF: 0.0333 AC: 5056 AN: 152034 Hom.: 282 Cov.: 32 AF XY: 0.0355 AC XY: 2639 AN XY: 74318

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.0185

Gnomad4 FIN AF: 0.00633

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0437

Alfa AF: 0.0223 Hom.: 38

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
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2273408; hg19: chr14-31061509; COSMIC: COSV52842108; COSMIC: COSV52842108;