rs34437789

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004260.4(RECQL4):c.1258+6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,611,922 control chromosomes in the GnomAD database, including 814 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 51 hom., cov: 34)

Exomes 𝑓: 0.030 ( 763 hom. )

Consequence

RECQL4
NM_004260.4 splice_region, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.371

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]

RECQL4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 8-144515758-T-A is Benign according to our data. Variant chr8-144515758-T-A is described in ClinVar as [Benign]. Clinvar id is 259257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144515758-T-A is described in Lovd as [Benign]. Variant chr8-144515758-T-A is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.1258+6A>T		splice_region_variant, intron_variant	Intron 6 of 20	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6 link	c.1258+6A>T		splice_region_variant, intron_variant	Intron 6 of 20	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3420

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00725

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0377

GnomAD3 exomes

AF:

0.0242

AC:

5958

AN:

246064

Hom.:

108

AF XY:

0.0249

AC XY:

3343

AN XY:

134110

show subpopulations

Gnomad AFR exome

AF:

0.00564

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0547

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.00862

Gnomad NFE exome

AF:

0.0345

Gnomad OTH exome

AF:

0.0319

GnomAD4 exome

AF:

0.0296

AC:

43153

AN:

1459668

Hom.:

763

Cov.:

AF XY:

0.0294

AC XY:

21375

AN XY:

726006

show subpopulations

Gnomad4 AFR exome

AF:

0.00822

Gnomad4 AMR exome

AF:

0.0202

Gnomad4 ASJ exome

AF:

0.0578

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0148

Gnomad4 FIN exome

AF:

0.00997

Gnomad4 NFE exome

AF:

0.0325

Gnomad4 OTH exome

AF:

0.0322

GnomAD4 genome

AF:

0.0224

AC:

3416

AN:

152254

Hom.:

Cov.:

AF XY:

0.0204

AC XY:

1520

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00609

Gnomad4 AMR

AF:

0.0283

Gnomad4 ASJ

AF:

0.0573

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.00725

Gnomad4 NFE

AF:

0.0323

Gnomad4 OTH

AF:

0.0373

Alfa

AF:

0.0310

Hom.:

Bravo

AF:

0.0240

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.0387

EpiControl

AF:

0.0392

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Baller-Gerold syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.1

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over