Variant 2-221426156-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004438.5(EPHA4):c.2847-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,601,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

EPHA4
NM_004438.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.619

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-221426156-G-A is Benign according to our data. Variant chr2-221426156-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1922209.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
EPHA4	NM_004438.5 linkuse as main transcript	c.2847-14C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000281821.7	NP_004429.1
EPHA4	NM_001304536.2 linkuse as main transcript	c.2847-14C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_001291465.1
EPHA4	NM_001304537.2 linkuse as main transcript	c.2694-14C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_001291466.1
EPHA4	NM_001363748.2 linkuse as main transcript	c.*26-14C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_001350677.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
EPHA4	ENST00000281821.7 linkuse as main transcript	c.2847-14C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_004438.5	ENSP00000281821	P1	P54764-1
EPHA4	ENST00000409854.5 linkuse as main transcript	c.*26-14C>T	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000386276
EPHA4	ENST00000409938.5 linkuse as main transcript	c.2847-14C>T	splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000386829	P1	P54764-1
EPHA4	ENST00000424339.1 linkuse as main transcript	c.*151-14C>T	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	2		ENSP00000408145

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249238

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000242

AC:

AN:

1448994

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

721596

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000209

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000197

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.5

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over