rs252818

Variant names:

• chr5-107389990-C-T
• rs252818
• NM_001962.3:c.419-2219G>A

Variant summary

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

The NM_001962.3(EFNA5):​c.419-2219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,140 control chromosomes in the GnomAD database, including 49,525 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 0.80 (49525 hom., cov: 32)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3	c.419-2219G>A		intron_variant	Intron 2 of 4	ENST00000333274.11	NP_001953.1
EFNA5	NM_001410773.1	c.419-2219G>A		intron_variant	Intron 2 of 3		NP_001397702.1
EFNA5	XM_011543250.4	c.365-2219G>A		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.419-2219G>A		intron_variant	Intron 2 of 4	1	NM_001962.3	ENSP00000328777.6
EFNA5	ENST00000509503.1	c.419-2219G>A		intron_variant	Intron 2 of 3	5		ENSP00000426989.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122151 AN: 152020 Hom.: 49467 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.804 AC: 122268 AN: 152140 Hom.: 49525 Cov.: 32 AF XY: 0.803 AC XY: 59737 AN XY: 74366

African (AFR) AF: 0.830 AC: 34441 AN: 41504

American (AMR) AF: 0.764 AC: 11674 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2874 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2629 AN: 5156

South Asian (SAS) AF: 0.735 AC: 3542 AN: 4822

European-Finnish (FIN) AF: 0.866 AC: 9186 AN: 10606

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55218 AN: 67992

Other (OTH) AF: 0.792 AC: 1669 AN: 2108

Alfa AF: 0.803 Hom.: 89413

Bravo AF: 0.800

Asia WGS AF: 0.671 AC: 2334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.024
DANN	Benign	0.42
PhyloP100		-3.0
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: rs252818; hg19: chr5-106725691;