Variant chr12-15681305-GTAA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The ENST00000281172.10(EPS8):c.60-6_60-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,058,244 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 27)

Exomes 𝑓: 0.018 ( 2 hom. )

Consequence

EPS8
ENST00000281172.10 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

EPS8 (HGNC:3420): (EGFR pathway substrate 8, signaling adaptor) This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as part of the EGFR pathway, though its exact role has not been determined. Highly similar proteins in other organisms are involved in the transduction of signals from Ras to Rac and growth factor-mediated actin remodeling. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

EPS8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-15681305-GTAA-G is Benign according to our data. Variant chr12-15681305-GTAA-G is described in ClinVar as [Benign]. Clinvar id is 769817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0025 (368/146948) while in subpopulation AFR AF= 0.00576 (230/39960). AF 95% confidence interval is 0.00515. There are 1 homozygotes in gnomad4. There are 173 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8	NM_004447.6 linkuse as main transcript	c.60-6_60-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000281172.10	NP_004438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10 linkuse as main transcript	c.60-6_60-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004447.6	ENSP00000281172	P1	Q12929-1

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

366

AN:

146920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00265

Gnomad ASJ

AF:

0.000292

Gnomad EAS

AF:

0.00275

Gnomad SAS

AF:

0.000430

Gnomad FIN

AF:

0.00209

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000868

Gnomad OTH

AF:

0.00150

GnomAD3 exomes

AF:

0.0106

AC:

1620

AN:

152932

Hom.:

AF XY:

0.0114

AC XY:

975

AN XY:

85482

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00562

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.00310

Gnomad SAS exome

AF:

0.0213

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.00958

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0177

AC:

16106

AN:

911296

Hom.:

AF XY:

0.0183

AC XY:

8362

AN XY:

457826

show subpopulations

Gnomad4 AFR exome

AF:

0.0169

Gnomad4 AMR exome

AF:

0.0156

Gnomad4 ASJ exome

AF:

0.0260

Gnomad4 EAS exome

AF:

0.0325

Gnomad4 SAS exome

AF:

0.0136

Gnomad4 FIN exome

AF:

0.0204

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0222

GnomAD4 genome

AF:

0.00250

AC:

368

AN:

146948

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

173

AN XY:

71474

show subpopulations

Gnomad4 AFR

AF:

0.00576

Gnomad4 AMR

AF:

0.00271

Gnomad4 ASJ

AF:

0.000292

Gnomad4 EAS

AF:

0.00296

Gnomad4 SAS

AF:

0.000431

Gnomad4 FIN

AF:

0.00209

Gnomad4 NFE

AF:

0.000868

Gnomad4 OTH

AF:

0.00149

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 06, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over