Variant 12-15681305-G-GTAATAATAA details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004447.6(EPS8):c.60-12_60-4dupTTATTATTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,083,770 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 4 hom., cov: 27)

Exomes 𝑓: 0.00086 ( 1 hom. )

Consequence

EPS8
NM_004447.6 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.197

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-G-GTAATAATAA is Benign according to our data. Variant chr12-15681305-G-GTAATAATAA is described in ClinVar as [Likely_benign]. Clinvar id is 724500.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 = 0.00533 (784/146968) while in subpopulation AFR AF= 0.0129 (517/39952). AF 95% confidence interval is 0.012. There are 4 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS8	NM_004447.6 link	c.60-12_60-4dupTTATTATTA		splice_region_variant, intron_variant	Intron 2 of 20	ENST00000281172.10	NP_004438.3	Q12929-1B4E3T6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10 link	c.60-4_60-3insTTATTATTA		splice_region_variant, intron_variant	Intron 2 of 20	1	NM_004447.6	ENSP00000281172.5		Q12929-1

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

781

AN:

146940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00163

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.00530

Gnomad SAS

AF:

0.000860

Gnomad FIN

AF:

0.00976

Gnomad MID

AF:

0.00327

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.00350

GnomAD3 exomes

AF:

0.000942

AC:

144

AN:

152932

Hom.:

AF XY:

0.000877

AC XY:

AN XY:

85482

show subpopulations

Gnomad AFR exome

AF:

0.000793

Gnomad AMR exome

AF:

0.000135

Gnomad ASJ exome

AF:

0.000845

Gnomad EAS exome

AF:

0.000238

Gnomad SAS exome

AF:

0.000402

Gnomad FIN exome

AF:

0.00473

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000860

AC:

806

AN:

936802

Hom.:

Cov.:

AF XY:

0.000854

AC XY:

403

AN XY:

471830

show subpopulations

Gnomad4 AFR exome

AF:

0.00408

Gnomad4 AMR exome

AF:

0.000535

Gnomad4 ASJ exome

AF:

0.000354

Gnomad4 EAS exome

AF:

0.00112

Gnomad4 SAS exome

AF:

0.000246

Gnomad4 FIN exome

AF:

0.00378

Gnomad4 NFE exome

AF:

0.000641

Gnomad4 OTH exome

AF:

0.00140

GnomAD4 genome

AF:

0.00533

AC:

784

AN:

146968

Hom.:

Cov.:

AF XY:

0.00574

AC XY:

410

AN XY:

71490

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00117

Gnomad4 EAS

AF:

0.00532

Gnomad4 SAS

AF:

0.000862

Gnomad4 FIN

AF:

0.00976

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.00348

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EPS8: BP4, BS1 -

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

EPS8-related disorder

Benign:1

May 03, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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