1-16152159-C-T

Position:

• chr1-16152159-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EPHA2	NM_004431.5	c.86-1196G>A		intron_variant		ENST00000358432.8	NP_004422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8	c.86-1196G>A		intron_variant		1	NM_004431.5	ENSP00000351209.5
EPHA2	ENST00000461614.1	n.206-3112G>A		intron_variant		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

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.550

Alfa AF: 0.587 Hom.: 24752

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

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

Other links and lift over

dbSNP: rs1472408; hg19: chr1-16478654;