5-107400656-C-T

Variant names:

• chr5-107400656-C-T
• rs252811
• NM_001962.3:c.419-12885G>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.419-12885G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,226 control chromosomes in the GnomAD database, including 49,740 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 0.81 (49740 hom., cov: 33)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNA5	NM_001962.3	MANE Select	c.419-12885G>A		intron	N/A	NP_001953.1	P52803
	EFNA5	NM_001410773.1		c.419-12885G>A		intron	N/A	NP_001397702.1	D6RDV5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNA5	ENST00000333274.11	TSL:1 MANE Select	c.419-12885G>A		intron	N/A	ENSP00000328777.6	P52803
	EFNA5	ENST00000509503.1	TSL:5	c.419-12885G>A		intron	N/A	ENSP00000426989.1	D6RDV5

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122432 AN: 152108 Hom.: 49683 Cov.: 33

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.793

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

GnomAD4 genome AF: 0.805 AC: 122548 AN: 152226 Hom.: 49740 Cov.: 33 AF XY: 0.805 AC XY: 59880 AN XY: 74418

African (AFR) AF: 0.832 AC: 34569 AN: 41528

American (AMR) AF: 0.766 AC: 11716 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2936 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2600 AN: 5172

South Asian (SAS) AF: 0.734 AC: 3544 AN: 4826

European-Finnish (FIN) AF: 0.867 AC: 9197 AN: 10612

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55275 AN: 68010

Other (OTH) AF: 0.793 AC: 1675 AN: 2112

Alfa AF: 0.807 Hom.: 162421

Bravo AF: 0.802

Asia WGS AF: 0.668 AC: 2326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.72
PhyloP100		0.23
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: rs252811; hg19: chr5-106736357;