dbSNP rs1065754: EPS15:p.Tyr443Tyr (chr1-51408279-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001981.3(EPS15):c.1329C>T(p.Tyr443Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,612,114 control chromosomes in the GnomAD database, including 389,759 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 0.74 ( 42897 hom., cov: 32)

Exomes 𝑓: 0.68 ( 346862 hom. )

Consequence

EPS15
NM_001981.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.665

Publications

28 publications found

Variant links:

Genes affected

EPS15 (HGNC:3419): (epidermal growth factor receptor pathway substrate 15) This gene encodes a protein that is part of the EGFR pathway. The protein is present at clatherin-coated pits and is involved in receptor-mediated endocytosis of EGF. Notably, this gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2009]

EPS15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=-0.665 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS15	NM_001981.3 link	c.1329C>T	p.Tyr443Tyr	synonymous_variant	Exon 15 of 25	ENST00000371733.8	NP_001972.1	P42566-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS15	ENST00000371733.8 link	c.1329C>T	p.Tyr443Tyr	synonymous_variant	Exon 15 of 25	1	NM_001981.3	ENSP00000360798.3		P42566-1

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

112741

AN:

151992

Hom.:

42833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.879

Gnomad AMI

AF:

0.599

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.575

Gnomad EAS

AF:

0.992

Gnomad SAS

AF:

0.782

Gnomad FIN

AF:

0.711

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.693

GnomAD2 exomes

AF:

0.732

AC:

183968

AN:

251432

AF XY:

0.722

show subpopulations

Gnomad AFR exome

AF:

0.881

Gnomad AMR exome

AF:

0.800

Gnomad ASJ exome

AF:

0.569

Gnomad EAS exome

AF:

0.993

Gnomad FIN exome

AF:

0.708

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.681

GnomAD4 exome

AF:

0.685

AC:

1000068

AN:

1460004

Hom.:

346862

Cov.:

AF XY:

0.686

AC XY:

498371

AN XY:

726452

show subpopulations

African (AFR)

AF:

0.879

AC:

29417

AN:

33464

American (AMR)

AF:

0.791

AC:

35391

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

14956

AN:

26116

East Asian (EAS)

AF:

0.990

AC:

39305

AN:

39692

South Asian (SAS)

AF:

0.762

AC:

65677

AN:

86236

European-Finnish (FIN)

AF:

0.710

AC:

37921

AN:

53414

Middle Eastern (MID)

AF:

0.590

AC:

3401

AN:

5768

European-Non Finnish (NFE)

AF:

0.659

AC:

732190

AN:

1110242

Other (OTH)

AF:

0.693

AC:

41810

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

15464

30928

46391

61855

77319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19200

38400

57600

76800

96000

<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:

0.742

AC:

112865

AN:

152110

Hom.:

42897

Cov.:

AF XY:

0.748

AC XY:

55587

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.879

AC:

36490

AN:

41530

American (AMR)

AF:

0.729

AC:

11135

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

1995

AN:

3470

East Asian (EAS)

AF:

0.992

AC:

5140

AN:

5180

South Asian (SAS)

AF:

0.781

AC:

3766

AN:

4820

European-Finnish (FIN)

AF:

0.711

AC:

7509

AN:

10556

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.657

AC:

44639

AN:

67960

Other (OTH)

AF:

0.697

AC:

1470

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1395

2789

4184

5578

6973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.689

Hom.:

41092

Bravo

AF:

0.749

Asia WGS

AF:

0.893

AC:

3105

AN:

3478

EpiCase

AF:

0.641

EpiControl

AF:

0.639

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.29

(source)

DANN

Benign

0.46

PhyloP100

-0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

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