1-16141429-G-T

Variant names:

• chr1-16141429-G-T
• rs3768293
• NM_004431.5:c.824-2999C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004431.5(EPHA2):​c.824-2999C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,172 control chromosomes in the GnomAD database, including 25,673 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 0.57 (25673 hom., cov: 34)
• Consequence: EPHA2 NM_004431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA2	NM_004431.5	c.824-2999C>A		intron_variant	Intron 3 of 16	ENST00000358432.8	NP_004422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8	c.824-2999C>A		intron_variant	Intron 3 of 16	1	NM_004431.5	ENSP00000351209.5
EPHA2	ENST00000480202.1	n.29-2999C>A		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87278 AN: 152054 Hom.: 25664 Cov.: 34

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.574 AC: 87322 AN: 152172 Hom.: 25673 Cov.: 34 AF XY: 0.577 AC XY: 42904 AN XY: 74396

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.554

Alfa AF: 0.590 Hom.: 34364

Bravo AF: 0.568

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.22
DANN	Benign	0.58

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: rs3768293; hg19: chr1-16467924;