rs10498112

Positions:

• chr2-221450021-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.1716-3840A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,298 control chromosomes in the GnomAD database, including 462 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 0.055 (462 hom., cov: 33)
• Consequence: EPHA4 NM_004438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA4	NM_004438.5	c.1716-3840A>G		intron_variant		ENST00000281821.7	NP_004429.1
EPHA4	NM_001304536.2	c.1716-3840A>G		intron_variant			NP_001291465.1
EPHA4	NM_001363748.2	c.1716-3840A>G		intron_variant			NP_001350677.1
EPHA4	NM_001304537.2	c.1563-3840A>G		intron_variant			NP_001291466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA4	ENST00000281821.7	c.1716-3840A>G		intron_variant		1	NM_004438.5	ENSP00000281821.2
EPHA4	ENST00000409854.5	c.1716-3840A>G		intron_variant		1		ENSP00000386276.1
EPHA4	ENST00000409938.5	c.1716-3840A>G		intron_variant		2		ENSP00000386829.1

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8424 AN: 152180 Hom.: 460 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.00593

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00607

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0555 AC: 8450 AN: 152298 Hom.: 462 Cov.: 33 AF XY: 0.0560 AC XY: 4173 AN XY: 74478

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0765

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.0909

Gnomad4 SAS AF: 0.0703

Gnomad4 FIN AF: 0.00593

Gnomad4 NFE AF: 0.00607

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0251 Hom.: 24

Bravo AF: 0.0660

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.6
DANN	Benign	0.48

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: rs10498112; hg19: chr2-222314741;