1-16148631-C-T

Position:

chr1-16148631-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004431.5(EPHA2):c.570G>A(p.Ala190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,607,538 control chromosomes in the GnomAD database, including 86,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6607 hom., cov: 33)

Exomes 𝑓: 0.32 ( 80147 hom. )

Consequence

EPHA2
NM_004431.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.73

Variant links:

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]

EPHA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 1-16148631-C-T is Benign according to our data. Variant chr1-16148631-C-T is described in ClinVar as [Benign]. Clinvar id is 259393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16148631-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA2	NM_004431.5 linkuse as main transcript	c.570G>A	p.Ala190=	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 linkuse as main transcript	c.570G>A	p.Ala190=	synonymous_variant	3/17	1	NM_004431.5	ENSP00000351209	P1	P29317-1
EPHA2	ENST00000461614.1 linkuse as main transcript	n.622G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42291

AN:

151930

Hom.:

6599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.333

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.320

GnomAD3 exomes

AF:

0.298

AC:

73497

AN:

246464

Hom.:

11871

AF XY:

0.306

AC XY:

40959

AN XY:

133724

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.0176

Gnomad SAS exome

AF:

0.336

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.324

AC:

472198

AN:

1455490

Hom.:

80147

Cov.:

AF XY:

0.326

AC XY:

236450

AN XY:

724346

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.402

Gnomad4 EAS exome

AF:

0.0238

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.339

Gnomad4 OTH exome

AF:

0.317

GnomAD4 genome

AF:

0.278

AC:

42310

AN:

152048

Hom.:

6607

Cov.:

AF XY:

0.277

AC XY:

20608

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.346

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.0239

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.274

Gnomad4 NFE

AF:

0.340

Gnomad4 OTH

AF:

0.322

Alfa

AF:

0.291

Hom.:

3112

Bravo

AF:

0.274

Asia WGS

AF:

0.192

AC:

668

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 6 multiple types

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 01, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.2

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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