chr3-135179860-G-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004441.5(EPHB1):c.1760G>C(p.Gly587Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000217 in 1,613,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
EPHB1
NM_004441.5 missense, splice_region
NM_004441.5 missense, splice_region
Scores
2
3
14
Splicing: ADA: 0.9894
1
1
Clinical Significance
Conservation
PhyloP100: 6.38
Genes affected
EPHB1 (HGNC:3392): (EPH receptor B1) Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. 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 divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene is a receptor for ephrin-B family members. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18023539).
BS2
?
High AC in GnomAdExome at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPHB1 | NM_004441.5 | c.1760G>C | p.Gly587Ala | missense_variant, splice_region_variant | 10/16 | ENST00000398015.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPHB1 | ENST00000398015.8 | c.1760G>C | p.Gly587Ala | missense_variant, splice_region_variant | 10/16 | 1 | NM_004441.5 | P1 | |
ENST00000649588.1 | n.329-21532C>G | intron_variant, non_coding_transcript_variant | |||||||
EPHB1 | ENST00000647596.1 | c.1760G>C | p.Gly587Ala | missense_variant, splice_region_variant | 10/16 | ||||
EPHB1 | ENST00000493838.1 | c.443G>C | p.Gly148Ala | missense_variant, splice_region_variant | 8/14 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152040Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000442 AC: 11AN: 249040Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135082
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461476Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 727018
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152040Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74266
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2023 | The c.1760G>C (p.G587A) alteration is located in exon 10 (coding exon 10) of the EPHB1 gene. This alteration results from a G to C substitution at nucleotide position 1760, causing the glycine (G) at amino acid position 587 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;.;T
Polyphen
B;.;.
Vest4
MutPred
Loss of methylation at R586 (P = 0.0609);Loss of methylation at R586 (P = 0.0609);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at