chr2-221418561-T-C

Position:

• chr2-221418561-T-C

Variant summary

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

The NM_004438.5(EPHA4):​c.*2811A>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 0.46 in 152,534 control chromosomes in the GnomAD database, including 16,833 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 0.46 (16796 hom., cov: 33)
  • Exomes 𝑓: 0.43 (37 hom.)
• Consequence: EPHA4 NM_004438.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376

Genes affected

EPHA4 (HGNC:3388): (EPH receptor A4) 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

EPHA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA4	NM_004438.5	c.*2811A>G		3_prime_UTR_variant	18/18	ENST00000281821.7	NP_004429.1
EPHA4	NM_001304536.2	c.*2811A>G		3_prime_UTR_variant	19/19		NP_001291465.1
EPHA4	NM_001363748.2	c.*2951A>G		3_prime_UTR_variant	18/18		NP_001350677.1
EPHA4	NM_001304537.2	c.*2811A>G		3_prime_UTR_variant	17/17		NP_001291466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA4	ENST00000281821	c.*2811A>G		3_prime_UTR_variant	18/18	1	NM_004438.5	ENSP00000281821.2
EPHA4	ENST00000469354.1	n.2359A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70000 AN: 151988 Hom.: 16779 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.425 AC: 182 AN: 428 Hom.: 37 Cov.: 0 AF XY: 0.450 AC XY: 116 AN XY: 258

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.460 AC: 70041 AN: 152106 Hom.: 16796 Cov.: 33 AF XY: 0.462 AC XY: 34342 AN XY: 74378

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.446

Alfa AF: 0.421 Hom.: 12775

Bravo AF: 0.459

Asia WGS AF: 0.359 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.78

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: rs3087584; hg19: chr2-222283281;