8-144513027-TGGTGCA-TGGTGCAGGTGCA
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2
The NM_004260.4(RECQL4):c.2569_2574dupTGCACC(p.Thr858_Arg859insCysThr) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,574,466 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004260.4 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2569_2574dupTGCACC | p.Thr858_Arg859insCysThr | conservative_inframe_insertion | Exon 15 of 21 | 1 | NM_004260.4 | ENSP00000482313.2 | ||
RECQL4 | ENST00000621189.4 | c.1498_1503dupTGCACC | p.Thr501_Arg502insCysThr | conservative_inframe_insertion | Exon 14 of 20 | 1 | ENSP00000483145.1 | |||
RECQL4 | ENST00000534626.6 | c.739_744dupTGCACC | p.Thr248_Arg249insCysThr | conservative_inframe_insertion | Exon 6 of 8 | 5 | ENSP00000477457.1 | |||
ENSG00000265393 | ENST00000580385.1 | n.271+205_271+210dupTGCAGG | intron_variant | Intron 1 of 1 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00353 AC: 537AN: 152196Hom.: 1 Cov.: 34
GnomAD3 exomes AF: 0.00195 AC: 365AN: 187612Hom.: 0 AF XY: 0.00189 AC XY: 192AN XY: 101586
GnomAD4 exome AF: 0.00255 AC: 3631AN: 1422152Hom.: 7 Cov.: 66 AF XY: 0.00248 AC XY: 1747AN XY: 703988
GnomAD4 genome AF: 0.00355 AC: 540AN: 152314Hom.: 1 Cov.: 34 AF XY: 0.00337 AC XY: 251AN XY: 74486
ClinVar
Submissions by phenotype
not provided Benign:3
RECQL4: PM4, BS1, BS2 -
This variant is associated with the following publications: (PMID: 27247962) -
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not specified Benign:2
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Rapadilino syndrome Benign:1
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Rothmund-Thomson syndrome type 2 Benign:1
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Baller-Gerold syndrome Benign:1
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Hereditary cancer-predisposing syndrome Benign:1
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RECQL4-related disorder Benign:1
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). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at