Genetic Variant EPHA1:p.Leu15Val (chr7-143408763-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005232.5(EPHA1):c.43C>G(p.Leu15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000035 in 1,143,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

EPHA1
NM_005232.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Publications

0 publications found

Variant links:

Genes affected

EPHA1 (HGNC:3385): (EPH receptor A1) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene is expressed in some human cancer cell lines and has been implicated in carcinogenesis. [provided by RefSeq, Jul 2008]

EPHA1 links:

EPHA1-AS1 (HGNC:27799): (EPHA1 antisense RNA 1)

EPHA1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17160752).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA1	NM_005232.5	MANE Select	c.43C>G	p.Leu15Val	missense	Exon 1 of 18	NP_005223.4
	EPHA1-AS1	NR_033897.1		n.74+877G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPHA1	ENST00000275815.4	TSL:1 MANE Select	c.43C>G	p.Leu15Val	missense	Exon 1 of 18	ENSP00000275815.3	P21709-1
EPHA1	ENST00000488068.5	TSL:1	n.43C>G		non_coding_transcript_exon	Exon 1 of 16
EPHA1-AS1	ENST00000429289.5	TSL:1	n.74+877G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

150976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000302

AC:

AN:

992674

Hom.:

Cov.:

AF XY:

0.00000212

AC XY:

AN XY:

471442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21050

American (AMR)

AF:

0.00

AC:

AN:

8186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13710

East Asian (EAS)

AF:

0.00

AC:

AN:

25952

South Asian (SAS)

AF:

0.00

AC:

AN:

17804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2742

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

841568

Other (OTH)

AF:

0.00

AC:

AN:

40628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000662

AC:

AN:

150976

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41016

American (AMR)

AF:

0.00

AC:

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67674

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.10

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.42

M_CAP

Benign

0.046

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.7

PhyloP100

1.3

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.40

REVEL

Benign

0.060

Sift

Benign

0.12

Sift4G

Benign

0.20

Polyphen

0.025

Vest4

0.22

MutPred

0.33

Loss of loop (P = 0.1242)

MVP

0.72

MPC

0.13

ClinPred

0.084

GERP RS

2.9

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.048

gMVP

0.37

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over