5-107630631-A-G

Variant names:

• chr5-107630631-A-G
• rs352602
• NM_001962.3:c.125+39858T>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+39858T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,904 control chromosomes in the GnomAD database, including 5,837 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 0.26 (5837 hom., cov: 30)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001962.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNA5	NM_001962.3	MANE Select	c.125+39858T>C		intron	N/A	NP_001953.1
	EFNA5	NM_001410773.1		c.125+39858T>C		intron	N/A	NP_001397702.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNA5	ENST00000333274.11	TSL:1 MANE Select	c.125+39858T>C		intron	N/A	ENSP00000328777.6
	EFNA5	ENST00000504941.1	TSL:1	n.397+39858T>C		intron	N/A
	EFNA5	ENST00000509503.1	TSL:5	c.125+39858T>C		intron	N/A	ENSP00000426989.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39910 AN: 151784 Hom.: 5834 Cov.: 30

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.263 AC: 39930 AN: 151904 Hom.: 5837 Cov.: 30 AF XY: 0.260 AC XY: 19317 AN XY: 74236

African (AFR) AF: 0.148 AC: 6151 AN: 41480

American (AMR) AF: 0.305 AC: 4650 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 862 AN: 3466

East Asian (EAS) AF: 0.122 AC: 631 AN: 5176

South Asian (SAS) AF: 0.165 AC: 795 AN: 4806

European-Finnish (FIN) AF: 0.315 AC: 3321 AN: 10536

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22338 AN: 67882

Other (OTH) AF: 0.283 AC: 594 AN: 2098

Alfa AF: 0.307 Hom.: 3942

Bravo AF: 0.261

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.51
PhyloP100		0.33
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: rs352602; hg19: chr5-106966332;