rs770700471
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The ENST00000358432.8(EPHA2):c.681C>T(p.Ala227=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
EPHA2
ENST00000358432.8 synonymous
ENST00000358432.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.04
Genes affected
EPHA2 (HGNC:3386): (EPH receptor A2) 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 encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.[provided by RefSeq, May 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 1-16148520-G-A is Benign according to our data. Variant chr1-16148520-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 468225.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-6.03 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000438 (64/1461200) while in subpopulation AMR AF= 0.000246 (11/44702). AF 95% confidence interval is 0.000137. There are 0 homozygotes in gnomad4_exome. There are 27 alleles in male gnomad4_exome subpopulation. Median coverage is 47. This position pass quality control queck.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EPHA2 | NM_004431.5 | c.681C>T | p.Ala227= | synonymous_variant | 3/17 | ENST00000358432.8 | NP_004422.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EPHA2 | ENST00000358432.8 | c.681C>T | p.Ala227= | synonymous_variant | 3/17 | 1 | NM_004431.5 | ENSP00000351209 | P1 | |
EPHA2 | ENST00000461614.1 | n.733C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152250Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
5
AN:
152250
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000519 AC: 13AN: 250712Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135614
GnomAD3 exomes
AF:
AC:
13
AN:
250712
Hom.:
AF XY:
AC XY:
4
AN XY:
135614
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461200Hom.: 0 Cov.: 47 AF XY: 0.0000371 AC XY: 27AN XY: 726924
GnomAD4 exome
AF:
AC:
64
AN:
1461200
Hom.:
Cov.:
47
AF XY:
AC XY:
27
AN XY:
726924
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74378
GnomAD4 genome
AF:
AC:
5
AN:
152250
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
74378
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cataract 6 multiple types Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 25, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at