Variant rs2230644 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004447.6(EPS8):c.213T>C(p.Thr71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,595,590 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 31 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 23 hom. )

Consequence

EPS8
NM_004447.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.350

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 12-15669817-A-G is Benign according to our data. Variant chr12-15669817-A-G is described in ClinVar as [Benign]. Clinvar id is 517549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.35 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00959 (1461/152340) while in subpopulation AFR AF= 0.0328 (1364/41572). AF 95% confidence interval is 0.0314. There are 31 homozygotes in gnomad4. There are 638 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8	NM_004447.6 linkuse as main transcript	c.213T>C	p.Thr71=	synonymous_variant	5/21	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.213T>C	p.Thr71=	synonymous_variant	5/21	1	NM_004447.6	ENSP00000281172	P1	Q12929-1

Frequencies

GnomAD3 genomes

AF:

0.00959

AC:

1460

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00278

AC:

656

AN:

236078

Hom.:

AF XY:

0.00218

AC XY:

279

AN XY:

127752

show subpopulations

Gnomad AFR exome

AF:

0.0348

Gnomad AMR exome

AF:

0.00207

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000360

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.00176

GnomAD4 exome

AF:

0.00102

AC:

1465

AN:

1443250

Hom.:

Cov.:

AF XY:

0.000911

AC XY:

653

AN XY:

717100

show subpopulations

Gnomad4 AFR exome

AF:

0.0321

Gnomad4 AMR exome

AF:

0.00218

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000719

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000143

Gnomad4 OTH exome

AF:

0.00275

GnomAD4 genome

AF:

0.00959

AC:

1461

AN:

152340

Hom.:

Cov.:

AF XY:

0.00856

AC XY:

638

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0328

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00543

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 14, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

p.Thr71Thr in exon 5 of EPS8: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 3.36% (341/10160) of A frican chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadi nstitute.org; dbSNP rs2230644). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.3

DANN

Benign

0.78

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