Genetic Variant EFNA5:c.125+95280T>C (chr5-107575209-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001962.3(EFNA5):c.125+95280T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,252 control chromosomes in the GnomAD database, including 2,798 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 0.18 ( 2798 hom., cov: 33)

Consequence

EFNA5
NM_001962.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.465

Publications

6 publications found

Variant links:

Genes affected

EFNA5 (HGNC:3225): (ephrin A5) Ephrin-A5, a member of the ephrin gene family, prevents axon bundling in cocultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, particularly in the nervous system. EPH receptors typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin ligands and receptors have been named by the Eph Nomenclature Committee (1997). Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are similarly divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. [provided by RefSeq, Jul 2008]

EFNA5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3 link	c.125+95280T>C		intron_variant	Intron 1 of 4	ENST00000333274.11	NP_001953.1	P52803
EFNA5	NM_001410773.1 link	c.125+95280T>C		intron_variant	Intron 1 of 3		NP_001397702.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EFNA5	ENST00000333274.11 link	c.125+95280T>C	intron_variant	Intron 1 of 4	1	NM_001962.3	ENSP00000328777.6	P52803
EFNA5	ENST00000504941.1 link	n.397+95280T>C	intron_variant	Intron 1 of 1	1
EFNA5	ENST00000509503.1 link	c.125+95280T>C	intron_variant	Intron 1 of 3	5		ENSP00000426989.1	D6RDV5

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26692

AN:

152134

Hom.:

2798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.00808

Gnomad SAS

AF:

0.0505

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.148

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

GnomAD4 genome

AF:

0.175

AC:

26719

AN:

152252

Hom.:

2798

Cov.:

AF XY:

0.172

AC XY:

12781

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.286

AC:

11869

AN:

41522

American (AMR)

AF:

0.111

AC:

1699

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

476

AN:

3470

East Asian (EAS)

AF:

0.00810

AC:

AN:

5186

South Asian (SAS)

AF:

0.0503

AC:

243

AN:

4832

European-Finnish (FIN)

AF:

0.149

AC:

1586

AN:

10616

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10256

AN:

68014

Other (OTH)

AF:

0.147

AC:

310

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1081

2163

3244

4326

5407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.135

Hom.:

999

Bravo

AF:

0.180

Asia WGS

AF:

0.0400

AC:

139

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.5

(source)

DANN

Benign

0.82

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over