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

Genomes: 𝑓 0.0035 ( 1 hom., cov: 34)
Exomes 𝑓: 0.0026 ( 7 hom. )

Consequence

RECQL4
NM_004260.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.833
Variant links:
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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_004260.4.
BP6
Variant 8-144513027-T-TGGTGCA is Benign according to our data. Variant chr8-144513027-T-TGGTGCA is described in ClinVar as [Likely_benign]. Clinvar id is 239738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00355 (540/152314) while in subpopulation AFR AF= 0.0064 (266/41574). AF 95% confidence interval is 0.00577. There are 1 homozygotes in gnomad4. There are 251 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RECQL4NM_004260.4 linkc.2569_2574dupTGCACC p.Thr858_Arg859insCysThr conservative_inframe_insertion Exon 15 of 21 ENST00000617875.6 NP_004251.4 O94761

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RECQL4ENST00000617875.6 linkc.2569_2574dupTGCACC p.Thr858_Arg859insCysThr conservative_inframe_insertion Exon 15 of 21 1 NM_004260.4 ENSP00000482313.2 O94761
RECQL4ENST00000621189.4 linkc.1498_1503dupTGCACC p.Thr501_Arg502insCysThr conservative_inframe_insertion Exon 14 of 20 1 ENSP00000483145.1 A0A087X072
RECQL4ENST00000534626.6 linkc.739_744dupTGCACC p.Thr248_Arg249insCysThr conservative_inframe_insertion Exon 6 of 8 5 ENSP00000477457.1 V9GZ64
ENSG00000265393ENST00000580385.1 linkn.271+205_271+210dupTGCAGG intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.00353
AC:
537
AN:
152196
Hom.:
1
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00634
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00445
Gnomad ASJ
AF:
0.00605
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00226
Gnomad OTH
AF:
0.00955
GnomAD3 exomes
AF:
0.00195
AC:
365
AN:
187612
Hom.:
0
AF XY:
0.00189
AC XY:
192
AN XY:
101586
show subpopulations
Gnomad AFR exome
AF:
0.00540
Gnomad AMR exome
AF:
0.00329
Gnomad ASJ exome
AF:
0.00652
Gnomad EAS exome
AF:
0.0000751
Gnomad SAS exome
AF:
0.000797
Gnomad FIN exome
AF:
0.000114
Gnomad NFE exome
AF:
0.00155
Gnomad OTH exome
AF:
0.00302
GnomAD4 exome
AF:
0.00255
AC:
3631
AN:
1422152
Hom.:
7
Cov.:
66
AF XY:
0.00248
AC XY:
1747
AN XY:
703988
show subpopulations
Gnomad4 AFR exome
AF:
0.00611
Gnomad4 AMR exome
AF:
0.00352
Gnomad4 ASJ exome
AF:
0.00712
Gnomad4 EAS exome
AF:
0.0000268
Gnomad4 SAS exome
AF:
0.000847
Gnomad4 FIN exome
AF:
0.000183
Gnomad4 NFE exome
AF:
0.00259
Gnomad4 OTH exome
AF:
0.00317
GnomAD4 genome
AF:
0.00355
AC:
540
AN:
152314
Hom.:
1
Cov.:
34
AF XY:
0.00337
AC XY:
251
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00640
Gnomad4 AMR
AF:
0.00444
Gnomad4 ASJ
AF:
0.00605
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.00226
Gnomad4 OTH
AF:
0.00945
Bravo
AF:
0.00413

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Jan 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

RECQL4: PM4, BS1, BS2 -

Nov 27, 2020
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27247962) -

Dec 05, 2016
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:2
Sep 13, 2021
Genetic Services Laboratory, University of Chicago
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jun 09, 2015
Eurofins Ntd Llc (ga)
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Rapadilino syndrome Benign:1
Feb 01, 2025
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Rothmund-Thomson syndrome type 2 Benign:1
Jul 07, 2023
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Baller-Gerold syndrome Benign:1
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1
May 02, 2021
Sema4, Sema4
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: curation

- -

RECQL4-related disorder Benign:1
May 22, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs548804317; hg19: chr8-145738410; API