Genetic Variant EFNA5:c.125+23630G>A (chr5-107646859-C-T) – 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+23630G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,822 control chromosomes in the GnomAD database, including 9,958 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 0.35 ( 9958 hom., cov: 32)

Consequence

EFNA5
NM_001962.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.203

Publications

14 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=-0.93).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3 link	c.125+23630G>A		intron_variant	Intron 1 of 4	ENST00000333274.11	NP_001953.1	P52803
EFNA5	NM_001410773.1 link	c.125+23630G>A		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+23630G>A	intron_variant	Intron 1 of 4	1	NM_001962.3	ENSP00000328777.6	P52803
EFNA5	ENST00000504941.1 link	n.397+23630G>A	intron_variant	Intron 1 of 1	1
EFNA5	ENST00000509503.1 link	c.125+23630G>A	intron_variant	Intron 1 of 3	5		ENSP00000426989.1	D6RDV5

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53516

AN:

151702

Hom.:

9949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.358

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

GnomAD4 genome

AF:

0.353

AC:

53550

AN:

151822

Hom.:

9958

Cov.:

AF XY:

0.353

AC XY:

26166

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.248

AC:

10262

AN:

41422

American (AMR)

AF:

0.348

AC:

5299

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

1339

AN:

3468

East Asian (EAS)

AF:

0.415

AC:

2140

AN:

5162

South Asian (SAS)

AF:

0.540

AC:

2596

AN:

4810

European-Finnish (FIN)

AF:

0.363

AC:

3814

AN:

10512

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.396

AC:

26913

AN:

67884

Other (OTH)

AF:

0.359

AC:

757

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1743

3486

5230

6973

8716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.385

Hom.:

49645

Bravo

AF:

0.343

Asia WGS

AF:

0.412

AC:

1431

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.76

(source)

DANN

Benign

0.22

PhyloP100

-0.20

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