7-100803477-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_004444.5(EPHB4):c.2948C>G(p.Pro983Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,575,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P983L) has been classified as Uncertain significance.
Frequency
Consequence
NM_004444.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPHB4 | NM_004444.5 | c.2948C>G | p.Pro983Arg | missense_variant | 17/17 | ENST00000358173.8 | |
EPHB4 | XM_017011816.2 | c.3002C>G | p.Pro1001Arg | missense_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPHB4 | ENST00000358173.8 | c.2948C>G | p.Pro983Arg | missense_variant | 17/17 | 1 | NM_004444.5 | P1 | |
EPHB4 | ENST00000360620.7 | c.2792C>G | p.Pro931Arg | missense_variant | 16/16 | 1 | |||
EPHB4 | ENST00000487222.5 | n.4149C>G | non_coding_transcript_exon_variant | 16/16 | 1 | ||||
EPHB4 | ENST00000616502.4 | c.*1413C>G | 3_prime_UTR_variant | 14/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000343 AC: 7AN: 204082Hom.: 0 AF XY: 0.0000275 AC XY: 3AN XY: 109280
GnomAD4 exome AF: 0.0000246 AC: 35AN: 1423286Hom.: 0 Cov.: 30 AF XY: 0.0000171 AC XY: 12AN XY: 702666
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74332
ClinVar
Submissions by phenotype
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2022 | This alteration is classified as likely 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at