rs12126436

Positions:

• chr1-22601179-G-A
• chr1-22601179-G-C

Variant summary

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

The NM_020526.5(EPHA8):​c.2729+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,530,784 control chromosomes in the GnomAD database, including 9,407 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 0.091 (809 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8598 hom.)
• Consequence: EPHA8 NM_020526.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA8	NM_020526.5	c.2729+91G>A		intron_variant		ENST00000166244.8	NP_065387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA8	ENST00000166244.8	c.2729+91G>A		intron_variant		2	NM_020526.5	ENSP00000166244	P1

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13753 AN: 151968 Hom.: 806 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0966

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.106 AC: 146671 AN: 1378698 Hom.: 8598 Cov.: 31 AF XY: 0.108 AC XY: 73132 AN XY: 679128

Gnomad4 AFR exome AF: 0.0280

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.0988

Gnomad4 EAS exome AF: 0.0198

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0966

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.0906 AC: 13778 AN: 152086 Hom.: 809 Cov.: 32 AF XY: 0.0931 AC XY: 6921 AN XY: 74320

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0966

Gnomad4 EAS AF: 0.0254

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0939

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0904 Hom.: 112

Bravo AF: 0.0948

Asia WGS AF: 0.100 AC: 349 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	0.12
DANN	Benign	0.82

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: rs12126436; hg19: chr1-22927672;