Genetic Variant EFNA5:c.126-86245A>G (chr5-107513754-T-C) – 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.126-86245A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,086 control chromosomes in the GnomAD database, including 1,998 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 0.13 ( 1998 hom., cov: 32)

Consequence

EFNA5
NM_001962.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.688

Publications

3 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3 link	c.126-86245A>G		intron_variant	Intron 1 of 4	ENST00000333274.11	NP_001953.1
EFNA5	NM_001410773.1 link	c.126-86245A>G		intron_variant	Intron 1 of 3		NP_001397702.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
EFNA5	ENST00000333274.11 link	c.126-86245A>G	intron_variant	Intron 1 of 4	1	NM_001962.3	ENSP00000328777.6
EFNA5	ENST00000504941.1 link	n.398-86245A>G	intron_variant	Intron 1 of 1	1
EFNA5	ENST00000509503.1 link	c.126-86245A>G	intron_variant	Intron 1 of 3	5		ENSP00000426989.1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20240

AN:

151968

Hom.:

1994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0728

Gnomad ASJ

AF:

0.0717

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.0863

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0851

Gnomad OTH

AF:

0.114

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

GnomAD4 genome

AF:

0.133

AC:

20272

AN:

152086

Hom.:

1998

Cov.:

AF XY:

0.129

AC XY:

9581

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.283

AC:

11722

AN:

41396

American (AMR)

AF:

0.0727

AC:

1111

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0717

AC:

249

AN:

3472

East Asian (EAS)

AF:

0.00289

AC:

AN:

5182

South Asian (SAS)

AF:

0.0350

AC:

169

AN:

4828

European-Finnish (FIN)

AF:

0.0863

AC:

915

AN:

10606

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0851

AC:

5784

AN:

67988

Other (OTH)

AF:

0.113

AC:

240

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

714

1428

2142

2856

3570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.0919

Hom.:

1478

Bravo

AF:

0.140

Asia WGS

AF:

0.0410

AC:

141

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.34

(source)

DANN

Benign

0.66

PhyloP100

-0.69

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