rs769426897
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_000553.6(WRN):c.1270-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,609,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_000553.6 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.1270-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.1270-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000553.6 | P1 | |||
WRN | ENST00000651642.1 | c.565-1471A>G | intron_variant | ||||||
WRN | ENST00000650667.1 | c.*884-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152012Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250848Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135688
GnomAD4 exome AF: 0.00000755 AC: 11AN: 1457636Hom.: 0 Cov.: 29 AF XY: 0.00000414 AC XY: 3AN XY: 725472
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152012Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74270
ClinVar
Submissions by phenotype
Werner syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at