8-116847501-T-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_006265.3(RAD21):āc.1895A>Gā(p.Ter632Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_006265.3 stop_retained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAD21 | NM_006265.3 | c.1895A>G | p.Ter632Ter | stop_retained_variant | Exon 14 of 14 | ENST00000297338.7 | NP_006256.1 | |
LOC112268030 | XR_002956724.2 | n.761-1387T>C | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000818 AC: 2AN: 244604Hom.: 0 AF XY: 0.00000757 AC XY: 1AN XY: 132128
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1453516Hom.: 0 Cov.: 30 AF XY: 0.00000415 AC XY: 3AN XY: 722600
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: RAD21 c.1895A>G alters a conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.2e-06 in 244604 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1895A>G in individuals affected with Cornelia De Lange Syndrome 4 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1991742). Based on the evidence outlined above, the variant was classified as likely benign. -
Cornelia de Lange syndrome 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at