1-16152159-C-T

Variant names:

• chr1-16152159-C-T
• rs1472408
• NM_004431.5:c.86-1196G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004431.5(EPHA2):​c.86-1196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,084 control chromosomes in the GnomAD database, including 24,616 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24616 hom., cov: 32)
• Consequence: EPHA2 NM_004431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• cataract 6 multiple types

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• early-onset non-syndromic cataract

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset posterior polar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset posterior subcapsular cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA2	NM_004431.5	c.86-1196G>A		intron_variant	Intron 1 of 16	ENST00000358432.8	NP_004422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8	c.86-1196G>A		intron_variant	Intron 1 of 16	1	NM_004431.5	ENSP00000351209.5
EPHA2	ENST00000461614.1	n.206-3112G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84553 AN: 151966 Hom.: 24606 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.552

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.556 AC: 84594 AN: 152084 Hom.: 24616 Cov.: 32 AF XY: 0.561 AC XY: 41676 AN XY: 74324

African (AFR) AF: 0.402 AC: 16679 AN: 41454

American (AMR) AF: 0.565 AC: 8635 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1766 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4625 AN: 5176

South Asian (SAS) AF: 0.575 AC: 2768 AN: 4818

European-Finnish (FIN) AF: 0.691 AC: 7321 AN: 10592

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40924 AN: 67966

Other (OTH) AF: 0.550 AC: 1163 AN: 2116

Alfa AF: 0.580 Hom.: 32048

Bravo AF: 0.545

Asia WGS AF: 0.684 AC: 2379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.7
DANN	Benign	0.86
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1472408; hg19: chr1-16478654;