dbSNP rs209698: EPHA8:c.*579A>G (chr1-22602320-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020526.5(EPHA8):c.*579A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 156,804 control chromosomes in the GnomAD database, including 12,363 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 0.39 ( 12332 hom., cov: 33)

Exomes 𝑓: 0.095 ( 31 hom. )

Consequence

EPHA8
NM_020526.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.52

Publications

4 publications found

Variant links:

Genes affected

EPHA8 (HGNC:3391): (EPH receptor A8) This gene encodes a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. The protein encoded by this gene functions as a receptor for ephrin A2, A3 and A5 and plays a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system. [provided by RefSeq, Jul 2008]

EPHA8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020526.5. 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
	EPHA8	NM_020526.5	MANE Select	c.*579A>G		3_prime_UTR	Exon 17 of 17	NP_065387.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA8	ENST00000166244.8	TSL:2 MANE Select	c.*579A>G		3_prime_UTR	Exon 17 of 17	ENSP00000166244.3

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59350

AN:

151808

Hom.:

12301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.378

GnomAD4 exome

AF:

0.0951

AC:

464

AN:

4878

Hom.:

Cov.:

AF XY:

0.103

AC XY:

253

AN XY:

2460

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.0690

AC:

AN:

116

Ashkenazi Jewish (ASJ)

AF:

0.0556

AC:

AN:

108

East Asian (EAS)

AF:

0.188

AC:

AN:

South Asian (SAS)

AF:

0.0897

AC:

AN:

156

European-Finnish (FIN)

AF:

0.219

AC:

103

AN:

470

Middle Eastern (MID)

AF:

0.111

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0791

AC:

292

AN:

3690

Other (OTH)

AF:

0.115

AC:

AN:

288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.391

AC:

59446

AN:

151926

Hom.:

12332

Cov.:

AF XY:

0.394

AC XY:

29254

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.524

AC:

21698

AN:

41432

American (AMR)

AF:

0.454

AC:

6934

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1070

AN:

3468

East Asian (EAS)

AF:

0.270

AC:

1389

AN:

5138

South Asian (SAS)

AF:

0.386

AC:

1859

AN:

4816

European-Finnish (FIN)

AF:

0.320

AC:

3390

AN:

10580

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21900

AN:

67894

Other (OTH)

AF:

0.380

AC:

802

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1830

3661

5491

7322

9152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.347

Hom.:

1972

Bravo

AF:

0.409

Asia WGS

AF:

0.342

AC:

1190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.34

(source)

DANN

Benign

0.34

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over