chr5-107388887-C-T

Variant names:

• chr5-107388887-C-T
• rs252817
• NM_001962.3:c.419-1116G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000333274.11(EFNA5):​c.419-1116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,908 control chromosomes in the GnomAD database, including 21,892 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 0.52 (21892 hom., cov: 31)
• Consequence: EFNA5 ENST00000333274.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 9 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000333274.11. 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.419-1116G>A		intron	N/A	NP_001953.1
	EFNA5	NM_001410773.1		c.419-1116G>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.419-1116G>A		intron	N/A	ENSP00000328777.6
	EFNA5	ENST00000509503.1	TSL:5	c.419-1116G>A		intron	N/A	ENSP00000426989.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78980 AN: 151790 Hom.: 21898 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.520 AC: 78998 AN: 151908 Hom.: 21892 Cov.: 31 AF XY: 0.512 AC XY: 38033 AN XY: 74232

African (AFR) AF: 0.373 AC: 15461 AN: 41412

American (AMR) AF: 0.495 AC: 7557 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2199 AN: 3466

East Asian (EAS) AF: 0.172 AC: 886 AN: 5162

South Asian (SAS) AF: 0.420 AC: 2025 AN: 4818

European-Finnish (FIN) AF: 0.567 AC: 5975 AN: 10540

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43092 AN: 67940

Other (OTH) AF: 0.520 AC: 1098 AN: 2112

Alfa AF: 0.592 Hom.: 92800

Bravo AF: 0.509

Asia WGS AF: 0.330 AC: 1150 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs252817; hg19: chr5-106724588; COSMIC: COSV60946701; COSMIC: COSV60946701;