chr5-107618844-A-T

Position:

• chr5-107618844-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001962.3(EFNA5):​c.125+51645T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,096 control chromosomes in the GnomAD database, including 2,982 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 0.17 (2982 hom., cov: 32)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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]

EFNA5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNA5	NM_001962.3	c.125+51645T>A		intron_variant		ENST00000333274.11	NP_001953.1
EFNA5	NM_001410773.1	c.125+51645T>A		intron_variant			NP_001397702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNA5	ENST00000333274.11	c.125+51645T>A		intron_variant		1	NM_001962.3	ENSP00000328777.6
EFNA5	ENST00000504941.1	n.397+51645T>A		intron_variant		1
EFNA5	ENST00000509503.1	c.125+51645T>A		intron_variant		5		ENSP00000426989.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26228 AN: 151978 Hom.: 2983 Cov.: 32

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.172 AC: 26230 AN: 152096 Hom.: 2982 Cov.: 32 AF XY: 0.177 AC XY: 13141 AN XY: 74346

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.203

Alfa AF: 0.0824 Hom.: 121

Bravo AF: 0.164

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs17160261; hg19: chr5-106954545;