rs6881619

Variant names:

• chr5-107573359-T-C
• rs6881619
• NM_001962.3:c.125+97130A>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.125+97130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 151,942 control chromosomes in the GnomAD database, including 2,343 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 0.14 (2343 hom., cov: 31)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3	c.125+97130A>G		intron_variant	Intron 1 of 4	ENST00000333274.11	NP_001953.1
EFNA5	NM_001410773.1	c.125+97130A>G		intron_variant	Intron 1 of 3		NP_001397702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNA5	ENST00000333274.11	c.125+97130A>G		intron_variant	Intron 1 of 4	1	NM_001962.3	ENSP00000328777.6
EFNA5	ENST00000504941.1	n.397+97130A>G		intron_variant	Intron 1 of 1	1
EFNA5	ENST00000509503.1	c.125+97130A>G		intron_variant	Intron 1 of 3	5		ENSP00000426989.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21444 AN: 151824 Hom.: 2340 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00737

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.0806

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0829

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.141 AC: 21478 AN: 151942 Hom.: 2343 Cov.: 31 AF XY: 0.138 AC XY: 10286 AN XY: 74284

African (AFR) AF: 0.307 AC: 12705 AN: 41396

American (AMR) AF: 0.0804 AC: 1227 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3468

East Asian (EAS) AF: 0.00738 AC: 38 AN: 5146

South Asian (SAS) AF: 0.0376 AC: 181 AN: 4814

European-Finnish (FIN) AF: 0.0806 AC: 852 AN: 10568

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0829 AC: 5637 AN: 67974

Other (OTH) AF: 0.116 AC: 245 AN: 2106

Alfa AF: 0.102 Hom.: 1995

Bravo AF: 0.152

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0090
DANN	Benign	0.33
PhyloP100		-1.9
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: rs6881619; hg19: chr5-106909060;