3-134951791-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_004441.5(EPHB1):c.544G>A(p.Ala182Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
EPHB1
NM_004441.5 missense
NM_004441.5 missense
Scores
8
4
7
Clinical Significance
Conservation
PhyloP100: 10.0
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 -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.898
BS2
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPHB1 | NM_004441.5 | c.544G>A | p.Ala182Thr | missense_variant | 3/16 | ENST00000398015.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPHB1 | ENST00000398015.8 | c.544G>A | p.Ala182Thr | missense_variant | 3/16 | 1 | NM_004441.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152206Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249264Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135210
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461714Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5AN XY: 727138
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74358
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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 | Aug 28, 2023 | The c.544G>A (p.A182T) alteration is located in exon 3 (coding exon 3) of the EPHB1 gene. This alteration results from a G to A substitution at nucleotide position 544, causing the alanine (A) at amino acid position 182 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Uncertain
D;.
Polyphen
D;.
Vest4
MutPred
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at