rs6603867

chr1-16148206-G-A

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.823+172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,040 control chromosomes in the GnomAD database, including 12,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (12972 hom., cov: 32)
• Consequence: EPHA2 NM_004431.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.136

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=-0.92).
• BP6: Variant 1-16148206-G-A is Benign according to our data. Variant chr1-16148206-G-A is described in ClinVar as [Benign]. Clinvar id is 1281636.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA2	NM_004431.5	c.823+172C>T		intron_variant		ENST00000358432.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA2	ENST00000358432.8	c.823+172C>T		intron_variant		1	NM_004431.5	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61213 AN: 151920 Hom.: 12948 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.0704

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.403 AC: 61290 AN: 152040 Hom.: 12972 Cov.: 32 AF XY: 0.399 AC XY: 29633 AN XY: 74330

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.0706

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.421

Alfa AF: 0.394 Hom.: 15227

Bravo AF: 0.410

Asia WGS AF: 0.251 AC: 873 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

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.30

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: rs6603867; hg19: chr1-16474701;