chr8-144511967-C-G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_004260.4(RECQL4):āc.3337G>Cā(p.Gly1113Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000632 in 1,611,598 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1113A) has been classified as Uncertain significance.
Frequency
Consequence
NM_004260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.3337G>C | p.Gly1113Arg | missense_variant | 19/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.3337G>C | p.Gly1113Arg | missense_variant | 19/21 | 1 | NM_004260.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00289 AC: 440AN: 152282Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.000805 AC: 198AN: 245862Hom.: 1 AF XY: 0.000671 AC XY: 90AN XY: 134226
GnomAD4 exome AF: 0.000393 AC: 574AN: 1459198Hom.: 4 Cov.: 57 AF XY: 0.000361 AC XY: 262AN XY: 725948
GnomAD4 genome AF: 0.00292 AC: 445AN: 152400Hom.: 0 Cov.: 35 AF XY: 0.00276 AC XY: 206AN XY: 74528
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 21, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | RECQL4: BP4 - |
not specified Benign:2Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 11, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 01, 2015 | - - |
Rothmund-Thomson syndrome type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 22, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
RECQL4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 08, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Baller-Gerold syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 09, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at