rs152611

Positions:

• chr5-107434606-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000333274.11(EFNA5):​c.126-7097T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,186 control chromosomes in the GnomAD database, including 4,950 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 0.25 (4950 hom., cov: 33)
• Consequence: EFNA5 ENST00000333274.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNA5	NM_001962.3	c.126-7097T>C		intron_variant		ENST00000333274.11	NP_001953.1
EFNA5	NM_001410773.1	c.126-7097T>C		intron_variant			NP_001397702.1
EFNA5	XM_011543250.4	c.72-7097T>C		intron_variant			XP_011541552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNA5	ENST00000333274.11	c.126-7097T>C		intron_variant		1	NM_001962.3	ENSP00000328777	P3
EFNA5	ENST00000504941.1	n.398-7097T>C		intron_variant, non_coding_transcript_variant		1
EFNA5	ENST00000509503.1	c.126-7097T>C		intron_variant		5		ENSP00000426989	A1
EFNA5	ENST00000505499.1	n.57-7097T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37685 AN: 152068 Hom.: 4948 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.248 AC: 37701 AN: 152186 Hom.: 4950 Cov.: 33 AF XY: 0.247 AC XY: 18366 AN XY: 74406

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.247

Alfa AF: 0.242 Hom.: 570

Bravo AF: 0.249

Asia WGS AF: 0.369 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs152611; hg19: chr5-106770307;