chr2-221442590-C-A

Position:

• chr2-221442590-C-A

Variant summary

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

The NM_004438.5(EPHA4):​c.2074+239G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,084 control chromosomes in the GnomAD database, including 50,281 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 0.81 (50281 hom., cov: 32)
• Consequence: EPHA4 NM_004438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614

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=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA4	NM_004438.5	c.2074+239G>T		intron_variant		ENST00000281821.7	NP_004429.1
EPHA4	NM_001304536.2	c.2074+239G>T		intron_variant			NP_001291465.1
EPHA4	NM_001304537.2	c.1921+239G>T		intron_variant			NP_001291466.1
EPHA4	NM_001363748.2	c.2074+239G>T		intron_variant			NP_001350677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA4	ENST00000281821.7	c.2074+239G>T		intron_variant		1	NM_004438.5	ENSP00000281821	P1
EPHA4	ENST00000409854.5	c.2074+239G>T		intron_variant		1		ENSP00000386276
EPHA4	ENST00000409938.5	c.2074+239G>T		intron_variant		2		ENSP00000386829	P1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123341 AN: 151966 Hom.: 50244 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.812 AC: 123433 AN: 152084 Hom.: 50281 Cov.: 32 AF XY: 0.814 AC XY: 60488 AN XY: 74354

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.981

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.806

Alfa AF: 0.813 Hom.: 85001

Bravo AF: 0.807

Asia WGS AF: 0.933 AC: 3240 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.68

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: rs2288629; hg19: chr2-222307310;