rs777881622
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000553.6(WRN):āc.4203A>Gā(p.Ala1401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,598 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 ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.000015 ( 0 hom. )
Consequence
WRN
NM_000553.6 synonymous
NM_000553.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.871
Genes affected
WRN (HGNC:12791): (WRN RecQ like helicase) This gene encodes a member of the RecQ subfamily of DNA helicase proteins. The encoded nuclear protein is important in the maintenance of genome stability and plays a role in DNA repair, replication, transcription and telomere maintenance. This protein contains a N-terminal 3' to 5' exonuclease domain, an ATP-dependent helicase domain and RQC (RecQ helicase conserved region) domain in its central region, and a C-terminal HRDC (helicase RNase D C-terminal) domain and nuclear localization signal. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by accelerated aging and an elevated risk for certain cancers. [provided by RefSeq, Aug 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 8-31173006-A-G is Benign according to our data. Variant chr8-31173006-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 238165.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.871 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.4203A>G | p.Ala1401= | synonymous_variant | 35/35 | ENST00000298139.7 | |
WRN | XM_011544639.4 | c.4122A>G | p.Ala1374= | synonymous_variant | 34/34 | ||
WRN | XM_011544640.2 | c.2604A>G | p.Ala868= | synonymous_variant | 23/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.4203A>G | p.Ala1401= | synonymous_variant | 35/35 | 1 | NM_000553.6 | P1 | |
ENST00000521252.1 | n.181+3686T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250662Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135596
GnomAD3 exomes
AF:
AC:
5
AN:
250662
Hom.:
AF XY:
AC XY:
2
AN XY:
135596
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461598Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727086
GnomAD4 exome
AF:
AC:
22
AN:
1461598
Hom.:
Cov.:
30
AF XY:
AC XY:
7
AN XY:
727086
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Werner syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at