NM_004260.4:c.18_26dupCGTGCGGGA
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4
The NM_004260.4(RECQL4):c.18_26dupCGTGCGGGA(p.Asp6_Arg8dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 1,313,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E9E) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Consequence
RECQL4
NM_004260.4 disruptive_inframe_insertion
NM_004260.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.49
Publications
0 publications found
Genes affected
RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_004260.4.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004260.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RECQL4 | NM_004260.4 | MANE Select | c.18_26dupCGTGCGGGA | p.Asp6_Arg8dup | disruptive_inframe_insertion | Exon 1 of 21 | NP_004251.4 | O94761 | |
| RECQL4 | NM_001413019.1 | c.18_26dupCGTGCGGGA | p.Asp6_Arg8dup | disruptive_inframe_insertion | Exon 1 of 20 | NP_001399948.1 | |||
| RECQL4 | NM_001413036.1 | c.18_26dupCGTGCGGGA | p.Asp6_Arg8dup | disruptive_inframe_insertion | Exon 1 of 21 | NP_001399965.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RECQL4 | ENST00000617875.6 | TSL:1 MANE Select | c.18_26dupCGTGCGGGA | p.Asp6_Arg8dup | disruptive_inframe_insertion | Exon 1 of 21 | ENSP00000482313.2 | O94761 | |
| RECQL4 | ENST00000621189.4 | TSL:1 | c.-1119_-1111dupCGTGCGGGA | 5_prime_UTR | Exon 1 of 20 | ENSP00000483145.1 | A0A087X072 | ||
| RECQL4 | ENST00000971710.1 | c.18_26dupCGTGCGGGA | p.Asp6_Arg8dup | disruptive_inframe_insertion | Exon 1 of 21 | ENSP00000641769.1 |
Frequencies
GnomAD3 genomes 0.00000663 AC: 1AN: 150894Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
150894
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000172 AC: 2AN: 1162814Hom.: 0 Cov.: 32 AF XY: 0.00000177 AC XY: 1AN XY: 565854 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1162814
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
565854
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
23208
American (AMR)
AF:
AC:
0
AN:
15416
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
17428
East Asian (EAS)
AF:
AC:
0
AN:
24674
South Asian (SAS)
AF:
AC:
0
AN:
45562
European-Finnish (FIN)
AF:
AC:
0
AN:
25930
Middle Eastern (MID)
AF:
AC:
0
AN:
3206
European-Non Finnish (NFE)
AF:
AC:
2
AN:
961140
Other (OTH)
AF:
AC:
0
AN:
46250
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000662 AC: 1AN: 151002Hom.: 0 Cov.: 34 AF XY: 0.0000136 AC XY: 1AN XY: 73752 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151002
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
73752
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41422
American (AMR)
AF:
AC:
0
AN:
15168
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3464
East Asian (EAS)
AF:
AC:
0
AN:
5160
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10084
Middle Eastern (MID)
AF:
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67572
Other (OTH)
AF:
AC:
0
AN:
2098
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Baller-Gerold syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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