chr5-107646859-C-T

Variant names:

• chr5-107646859-C-T
• rs10074258
• NM_001962.3:c.125+23630G>A

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+23630G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,822 control chromosomes in the GnomAD database, including 9,958 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 0.35 (9958 hom., cov: 32)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 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+23630G>A		intron	N/A	NP_001953.1
	EFNA5	NM_001410773.1		c.125+23630G>A		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+23630G>A		intron	N/A	ENSP00000328777.6
	EFNA5	ENST00000504941.1	TSL:1	n.397+23630G>A		intron	N/A
	EFNA5	ENST00000509503.1	TSL:5	c.125+23630G>A		intron	N/A	ENSP00000426989.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53516 AN: 151702 Hom.: 9949 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.353 AC: 53550 AN: 151822 Hom.: 9958 Cov.: 32 AF XY: 0.353 AC XY: 26166 AN XY: 74172

African (AFR) AF: 0.248 AC: 10262 AN: 41422

American (AMR) AF: 0.348 AC: 5299 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3468

East Asian (EAS) AF: 0.415 AC: 2140 AN: 5162

South Asian (SAS) AF: 0.540 AC: 2596 AN: 4810

European-Finnish (FIN) AF: 0.363 AC: 3814 AN: 10512

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26913 AN: 67884

Other (OTH) AF: 0.359 AC: 757 AN: 2110

Alfa AF: 0.385 Hom.: 49645

Bravo AF: 0.343

Asia WGS AF: 0.412 AC: 1431 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.76
DANN	Benign	0.22
PhyloP100		-0.20
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: rs10074258; hg19: chr5-106982560;