5-107473232-C-G

Variant names:

• chr5-107473232-C-G
• rs153690
• NM_001962.3:c.126-45723G>C

Variant summary

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

The NM_001962.3(EFNA5):​c.126-45723G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 150,672 control chromosomes in the GnomAD database, including 17,277 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 0.47 (17277 hom., cov: 28)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3	c.126-45723G>C		intron_variant	Intron 1 of 4	ENST00000333274.11	NP_001953.1
EFNA5	NM_001410773.1	c.126-45723G>C		intron_variant	Intron 1 of 3		NP_001397702.1
EFNA5	XM_011543250.4	c.71+20671G>C		intron_variant	Intron 1 of 4		XP_011541552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNA5	ENST00000333274.11	c.126-45723G>C		intron_variant	Intron 1 of 4	1	NM_001962.3	ENSP00000328777.6
EFNA5	ENST00000504941.1	n.398-45723G>C		intron_variant	Intron 1 of 1	1
EFNA5	ENST00000509503.1	c.126-45723G>C		intron_variant	Intron 1 of 3	5		ENSP00000426989.1
EFNA5	ENST00000505499.1	n.56+32904G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71124 AN: 150572 Hom.: 17275 Cov.: 28

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.472 AC: 71138 AN: 150672 Hom.: 17277 Cov.: 28 AF XY: 0.468 AC XY: 34372 AN XY: 73392

African (AFR) AF: 0.388 AC: 15883 AN: 40888

American (AMR) AF: 0.435 AC: 6581 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1840 AN: 3468

East Asian (EAS) AF: 0.375 AC: 1909 AN: 5086

South Asian (SAS) AF: 0.555 AC: 2663 AN: 4796

European-Finnish (FIN) AF: 0.423 AC: 4290 AN: 10136

Middle Eastern (MID) AF: 0.517 AC: 150 AN: 290

European-Non Finnish (NFE) AF: 0.536 AC: 36339 AN: 67858

Other (OTH) AF: 0.494 AC: 1036 AN: 2096

Alfa AF: 0.482 Hom.: 2188

Bravo AF: 0.472

Asia WGS AF: 0.444 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.65
PhyloP100		0.13
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: rs153690; hg19: chr5-106808933; COSMIC: COSV60945864;