7-100803476-C-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004444.5(EPHB4):c.2949G>T(p.Pro983Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,575,352 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 117 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 136 hom. )
Consequence
EPHB4
NM_004444.5 synonymous
NM_004444.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.555
Genes affected
EPHB4 (HGNC:3395): (EPH receptor B4) 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 binds to ephrin-B2 and plays an essential role in vascular development. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 7-100803476-C-A is Benign according to our data. Variant chr7-100803476-C-A is described in ClinVar as [Benign]. Clinvar id is 811022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-100803476-C-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.555 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EPHB4 | NM_004444.5 | c.2949G>T | p.Pro983Pro | synonymous_variant | 17/17 | ENST00000358173.8 | NP_004435.3 | |
EPHB4 | XM_017011816.2 | c.3003G>T | p.Pro1001Pro | synonymous_variant | 17/17 | XP_016867305.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EPHB4 | ENST00000358173.8 | c.2949G>T | p.Pro983Pro | synonymous_variant | 17/17 | 1 | NM_004444.5 | ENSP00000350896.3 | ||
EPHB4 | ENST00000360620.7 | c.2793G>T | p.Pro931Pro | synonymous_variant | 16/16 | 1 | ENSP00000353833.3 | |||
EPHB4 | ENST00000487222.5 | n.4150G>T | non_coding_transcript_exon_variant | 16/16 | 1 | |||||
EPHB4 | ENST00000616502.4 | c.*1414G>T | 3_prime_UTR_variant | 14/14 | 5 | ENSP00000482702.1 |
Frequencies
GnomAD3 genomes AF: 0.0231 AC: 3509AN: 152170Hom.: 115 Cov.: 32
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GnomAD3 exomes AF: 0.00741 AC: 1506AN: 203110Hom.: 40 AF XY: 0.00656 AC XY: 714AN XY: 108778
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GnomAD4 exome AF: 0.00335 AC: 4762AN: 1423064Hom.: 136 Cov.: 30 AF XY: 0.00335 AC XY: 2356AN XY: 702568
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GnomAD4 genome AF: 0.0231 AC: 3524AN: 152288Hom.: 117 Cov.: 32 AF XY: 0.0231 AC XY: 1717AN XY: 74476
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 06, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 16, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2020 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at