rs6888194

Variant names:

• chr5-107574956-T-C
• rs6888194
• NM_001962.3:c.125+95533A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-107574956-T-C
• chr5-107574956-T-G

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+95533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,122 control chromosomes in the GnomAD database, including 5,903 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 0.23 (5903 hom., cov: 32)
• Consequence: EFNA5 NM_001962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA5	NM_001962.3	c.125+95533A>G		intron_variant	Intron 1 of 4	ENST00000333274.11	NP_001953.1
EFNA5	NM_001410773.1	c.125+95533A>G		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+95533A>G		intron_variant	Intron 1 of 4	1	NM_001962.3	ENSP00000328777.6
EFNA5	ENST00000504941.1	n.397+95533A>G		intron_variant	Intron 1 of 1	1
EFNA5	ENST00000509503.1	c.125+95533A>G		intron_variant	Intron 1 of 3	5		ENSP00000426989.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35051 AN: 152006 Hom.: 5894 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.00830

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.231 AC: 35098 AN: 152122 Hom.: 5903 Cov.: 32 AF XY: 0.225 AC XY: 16720 AN XY: 74372

African (AFR) AF: 0.476 AC: 19753 AN: 41460

American (AMR) AF: 0.131 AC: 2009 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3470

East Asian (EAS) AF: 0.00832 AC: 43 AN: 5168

South Asian (SAS) AF: 0.0510 AC: 246 AN: 4826

European-Finnish (FIN) AF: 0.149 AC: 1579 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10333 AN: 67994

Other (OTH) AF: 0.187 AC: 395 AN: 2110

Alfa AF: 0.131 Hom.: 362

Bravo AF: 0.242

Asia WGS AF: 0.0540 AC: 187 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.66
PhyloP100		0.14
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: rs6888194; hg19: chr5-106910657;