rs209693

Positions:

• chr1-22595533-T-G

Variant summary

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

The NM_020526.5(EPHA8):​c.1697+210T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,038 control chromosomes in the GnomAD database, including 15,965 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 0.44 (15965 hom., cov: 32)
• Consequence: EPHA8 NM_020526.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA8	NM_020526.5	c.1697+210T>G		intron_variant		ENST00000166244.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA8	ENST00000166244.8	c.1697+210T>G		intron_variant		2	NM_020526.5	P1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66118 AN: 151920 Hom.: 15926 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.436 AC: 66219 AN: 152038 Hom.: 15965 Cov.: 32 AF XY: 0.435 AC XY: 32360 AN XY: 74328

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.405

Alfa AF: 0.370 Hom.: 5727

Bravo AF: 0.454

Asia WGS AF: 0.373 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.1
DANN	Benign	0.66

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: rs209693; hg19: chr1-22922026;