chr21-36413102-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005441.3(CHAF1B):c.1280C>T(p.Pro427Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005441.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHAF1B | NM_005441.3 | c.1280C>T | p.Pro427Leu | missense_variant | 12/14 | ENST00000314103.6 | |
CHAF1B | XM_047441000.1 | c.719C>T | p.Pro240Leu | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHAF1B | ENST00000314103.6 | c.1280C>T | p.Pro427Leu | missense_variant | 12/14 | 1 | NM_005441.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000227 AC: 57AN: 251206Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135806
GnomAD4 exome AF: 0.000202 AC: 296AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.000180 AC XY: 131AN XY: 727246
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74292
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 06, 2023 | The c.1280C>T (p.P427L) alteration is located in exon 12 (coding exon 11) of the CHAF1B gene. This alteration results from a C to T substitution at nucleotide position 1280, causing the proline (P) at amino acid position 427 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at