rs252817

chr5-107388887-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001962.3(EFNA5):c.419-1116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,908 control chromosomes in the GnomAD database, including 21,892 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 0.52 (21892 hom., cov: 31)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNA5	NM_001962.3	c.419-1116G>A		intron_variant		ENST00000333274.11
EFNA5	NM_001410773.1	c.419-1116G>A		intron_variant
EFNA5	XM_011543250.4	c.365-1116G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNA5	ENST00000333274.11	c.419-1116G>A		intron_variant		1	NM_001962.3	P3
EFNA5	ENST00000509503.1	c.419-1116G>A		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78980 AN: 151790 Hom.: 21898 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.520 AC: 78998 AN: 151908 Hom.: 21892 Cov.: 31 AF XY: 0.512 AC XY: 38033 AN XY: 74232

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.520

Alfa AF: 0.605 Hom.: 43655

Bravo AF: 0.509

Asia WGS AF: 0.330 AC: 1150 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	13
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs252817; hg19: chr5-106724588; COSMIC: COSV60946701; COSMIC: COSV60946701;