dbSNP rs1462823087: EPHA1:p.Pro20Leu (chr7-143408747-G-A) – 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.59C>T(p.Pro20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000667 in 899,938 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P20H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

EPHA1
NM_005232.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.432

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:

Genome browser will be placed here

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=0.09641969).

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.59C>T	p.Pro20Leu	missense	Exon 1 of 18	NP_005223.4
	EPHA1-AS1	NR_033897.1		n.74+861G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPHA1	ENST00000275815.4	TSL:1 MANE Select	c.59C>T	p.Pro20Leu	missense	Exon 1 of 18	ENSP00000275815.3	P21709-1
EPHA1	ENST00000488068.5	TSL:1	n.59C>T		non_coding_transcript_exon	Exon 1 of 16
EPHA1-AS1	ENST00000429289.5	TSL:1	n.74+861G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000667

AC:

AN:

899938

Hom.:

Cov.:

AF XY:

0.00000466

AC XY:

AN XY:

429178

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19142

American (AMR)

AF:

0.00

AC:

AN:

8052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13094

East Asian (EAS)

AF:

0.00

AC:

AN:

25502

South Asian (SAS)

AF:

0.00

AC:

AN:

16146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2570

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

756814

Other (OTH)

AF:

0.000159

AC:

AN:

37630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.039

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.20

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

0.43

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.33

REVEL

Benign

0.049

Sift

Benign

0.71

Sift4G

Benign

0.70

Polyphen

0.0010

Vest4

0.27

MutPred

0.37

Loss of catalytic residue at P20 (P = 0.0456)

MVP

0.54

MPC

0.14

ClinPred

0.15

GERP RS

1.8

PromoterAI

-0.0037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.042

gMVP

0.32

Mutation Taster

=88/12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over