rs209698

Positions:

• chr1-22602320-A-G

Variant summary

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

The NM_020526.5(EPHA8):​c.*579A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 156,804 control chromosomes in the GnomAD database, including 12,363 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 0.39 (12332 hom., cov: 33)
  • Exomes 𝑓: 0.095 (31 hom.)
• Consequence: EPHA8 NM_020526.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

Genes affected

EPHA8 (HGNC:3391): (EPH receptor A8) This gene encodes a member of 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. The protein encoded by this gene functions as a receptor for ephrin A2, A3 and A5 and plays a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA8	NM_020526.5	c.*579A>G		3_prime_UTR_variant	17/17	ENST00000166244.8	NP_065387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA8	ENST00000166244.8	c.*579A>G		3_prime_UTR_variant	17/17	2	NM_020526.5	ENSP00000166244	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59350 AN: 151808 Hom.: 12301 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.378

GnomAD4 exome AF: 0.0951 AC: 464 AN: 4878 Hom.: 31 Cov.: 0 AF XY: 0.103 AC XY: 253 AN XY: 2460

Gnomad4 AMR exome AF: 0.0690

Gnomad4 ASJ exome AF: 0.0556

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.0897

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.0791

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.391 AC: 59446 AN: 151926 Hom.: 12332 Cov.: 33 AF XY: 0.394 AC XY: 29254 AN XY: 74266

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.380

Alfa AF: 0.347 Hom.: 1972

Bravo AF: 0.409

Asia WGS AF: 0.342 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.34
DANN	Benign	0.34

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: rs209698; hg19: chr1-22928813; COSMIC: COSV51282681;