rs252984

Variant names:

• chr5-107416636-T-C
• rs252984
• NM_001962.3:c.418+10581A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001962.3(EFNA5):​c.418+10581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,142 control chromosomes in the GnomAD database, including 47,587 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 0.79 (47587 hom., cov: 33)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3	c.418+10581A>G		intron_variant	Intron 2 of 4	ENST00000333274.11	NP_001953.1
EFNA5	NM_001410773.1	c.418+10581A>G		intron_variant	Intron 2 of 3		NP_001397702.1
EFNA5	XM_011543250.4	c.364+10581A>G		intron_variant	Intron 2 of 4		XP_011541552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNA5	ENST00000333274.11	c.418+10581A>G		intron_variant	Intron 2 of 4	1	NM_001962.3	ENSP00000328777.6
EFNA5	ENST00000509503.1	c.418+10581A>G		intron_variant	Intron 2 of 3	5		ENSP00000426989.1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119723 AN: 152024 Hom.: 47541 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.788 AC: 119828 AN: 152142 Hom.: 47587 Cov.: 33 AF XY: 0.788 AC XY: 58599 AN XY: 74370

African (AFR) AF: 0.774 AC: 32129 AN: 41500

American (AMR) AF: 0.759 AC: 11593 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2938 AN: 3470

East Asian (EAS) AF: 0.492 AC: 2547 AN: 5176

South Asian (SAS) AF: 0.735 AC: 3550 AN: 4828

European-Finnish (FIN) AF: 0.866 AC: 9171 AN: 10584

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55222 AN: 67980

Other (OTH) AF: 0.777 AC: 1645 AN: 2116

Alfa AF: 0.796 Hom.: 8178

Bravo AF: 0.782

Asia WGS AF: 0.658 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.61
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs252984; hg19: chr5-106752337; COSMIC: COSV60954980;