rs13375644

Positions:

• chr1-16135338-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004431.5(EPHA2):​c.1429-149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 1,065,972 control chromosomes in the GnomAD database, including 9,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (4693 hom., cov: 32)
  • Exomes 𝑓: 0.068 (4386 hom.)
• Consequence: EPHA2 NM_004431.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.209

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-16135338-C-T is Benign according to our data. Variant chr1-16135338-C-T is described in ClinVar as [Benign]. Clinvar id is 1250222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA2	NM_004431.5	c.1429-149G>A		intron_variant		ENST00000358432.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA2	ENST00000358432.8	c.1429-149G>A		intron_variant		1	NM_004431.5	P1
EPHA2	ENST00000480202.1	n.634-149G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26483 AN: 151970 Hom.: 4672 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.0676 AC: 61780 AN: 913884 Hom.: 4386 AF XY: 0.0674 AC XY: 31501 AN XY: 467424

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.0897

Gnomad4 ASJ exome AF: 0.0719

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0681

Gnomad4 NFE exome AF: 0.0452

Gnomad4 OTH exome AF: 0.0885

GnomAD4 genome AF: 0.175 AC: 26547 AN: 152088 Hom.: 4693 Cov.: 32 AF XY: 0.174 AC XY: 12904 AN XY: 74370

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0757

Gnomad4 NFE AF: 0.0491

Gnomad4 OTH AF: 0.147

Alfa AF: 0.125 Hom.: 499

Bravo AF: 0.192

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs13375644; hg19: chr1-16461833;