Genetic Variant EFNA5:c.125+51645T>A (chr5-107618844-A-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+51645T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,096 control chromosomes in the GnomAD database, including 2,982 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 0.17 ( 2982 hom., cov: 32)

Consequence

EFNA5
NM_001962.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

Publications

5 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3 link	c.125+51645T>A		intron_variant	Intron 1 of 4	ENST00000333274.11	NP_001953.1	P52803
EFNA5	NM_001410773.1 link	c.125+51645T>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+51645T>A	intron_variant	Intron 1 of 4	1	NM_001962.3	ENSP00000328777.6	P52803
EFNA5	ENST00000504941.1 link	n.397+51645T>A	intron_variant	Intron 1 of 1	1
EFNA5	ENST00000509503.1 link	c.125+51645T>A	intron_variant	Intron 1 of 3	5		ENSP00000426989.1	D6RDV5

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26228

AN:

151978

Hom.:

2983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.204

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

GnomAD4 genome

AF:

0.172

AC:

26230

AN:

152096

Hom.:

2982

Cov.:

AF XY:

0.177

AC XY:

13141

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0476

AC:

1976

AN:

41506

American (AMR)

AF:

0.189

AC:

2888

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

1174

AN:

3468

East Asian (EAS)

AF:

0.390

AC:

2016

AN:

5164

South Asian (SAS)

AF:

0.419

AC:

2013

AN:

4810

European-Finnish (FIN)

AF:

0.179

AC:

1888

AN:

10566

Middle Eastern (MID)

AF:

0.236

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.201

AC:

13679

AN:

67980

Other (OTH)

AF:

0.203

AC:

429

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1052

2104

3157

4209

5261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.0824

Hom.:

121

Bravo

AF:

0.164

Asia WGS

AF:

0.323

AC:

1122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.9

(source)

DANN

Benign

0.58

PhyloP100

0.015

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