5-107618844-A-T

Variant names:

• chr5-107618844-A-T
• rs17160261
• NM_001962.3:c.125+51645T>A

Variant summary

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

The ENST00000333274.11(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 ENST00000333274.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 5 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 (SAS) allele frequency at 95% confidence interval = 0.403 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.125+51645T>A		intron	N/A	NP_001953.1
	EFNA5	NM_001410773.1		c.125+51645T>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+51645T>A		intron	N/A	ENSP00000328777.6
	EFNA5	ENST00000504941.1	TSL:1	n.397+51645T>A		intron	N/A
	EFNA5	ENST00000509503.1	TSL:5	c.125+51645T>A		intron	N/A	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

African (AFR) AF: 0.0476 AC: 1976 AN: 41506

American (AMR) AF: 0.189 AC: 2888 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1174 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2016 AN: 5164

South Asian (SAS) AF: 0.419 AC: 2013 AN: 4810

European-Finnish (FIN) AF: 0.179 AC: 1888 AN: 10566

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.201 AC: 13679 AN: 67980

Other (OTH) AF: 0.203 AC: 429 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.58
PhyloP100		0.015
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: rs17160261; hg19: chr5-106954545;