NM_001962.3:c.125+95280T>C

Variant names:

• chr5-107575209-A-G
• rs12519552
• NM_001962.3:c.125+95280T>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.125+95280T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,252 control chromosomes in the GnomAD database, including 2,798 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 0.18 (2798 hom., cov: 33)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465
• Publications: 6 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3	c.125+95280T>C		intron_variant	Intron 1 of 4	ENST00000333274.11	NP_001953.1
EFNA5	NM_001410773.1	c.125+95280T>C		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+95280T>C		intron_variant	Intron 1 of 4	1	NM_001962.3	ENSP00000328777.6
EFNA5	ENST00000504941.1	n.397+95280T>C		intron_variant	Intron 1 of 1	1
EFNA5	ENST00000509503.1	c.125+95280T>C		intron_variant	Intron 1 of 3	5		ENSP00000426989.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26692 AN: 152134 Hom.: 2798 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00808

Gnomad SAS AF: 0.0505

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.175 AC: 26719 AN: 152252 Hom.: 2798 Cov.: 33 AF XY: 0.172 AC XY: 12781 AN XY: 74436

African (AFR) AF: 0.286 AC: 11869 AN: 41522

American (AMR) AF: 0.111 AC: 1699 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.00810 AC: 42 AN: 5186

South Asian (SAS) AF: 0.0503 AC: 243 AN: 4832

European-Finnish (FIN) AF: 0.149 AC: 1586 AN: 10616

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10256 AN: 68014

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.135 Hom.: 999

Bravo AF: 0.180

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.82
PhyloP100		0.47
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: rs12519552; hg19: chr5-106910910;