NM_004260.4:c.1621-8A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004260.4(RECQL4):c.1621-8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000762 in 1,609,830 control chromosomes in the GnomAD database, including 11 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00080 ( 3 hom., cov: 34)

Exomes 𝑓: 0.00076 ( 8 hom. )

Consequence

RECQL4
NM_004260.4 splice_region, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.56

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 8-144514533-T-C is Benign according to our data. Variant chr8-144514533-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 239701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514533-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000758 (1105/1457834) while in subpopulation MID AF= 0.00678 (39/5756). AF 95% confidence interval is 0.00592. There are 8 homozygotes in gnomad4_exome. There are 720 alleles in male gnomad4_exome subpopulation. Median coverage is 36. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.1621-8A>G		splice_region_variant, intron_variant	Intron 9 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.1621-8A>G		splice_region_variant, intron_variant	Intron 9 of 20	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.000810

AC:

123

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00135

AC:

329

AN:

243254

Hom.:

AF XY:

0.00172

AC XY:

228

AN XY:

132858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00133

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00628

Gnomad FIN exome

AF:

0.0000948

Gnomad NFE exome

AF:

0.000591

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.000758

AC:

1105

AN:

1457834

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

720

AN XY:

725000

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.00108

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00636

Gnomad4 FIN exome

AF:

0.0000387

Gnomad4 NFE exome

AF:

0.000321

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.000796

AC:

121

AN:

151996

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000733

Hom.:

Bravo

AF:

0.000733

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RECQL4: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:2

Jun 07, 2022

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 07, 2017

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: 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

Apr 30, 2021

Sema4, Sema4

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.14

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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