8-144514540-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004260.4(RECQL4):c.1621-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,607,346 control chromosomes in the GnomAD database, including 175,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13353 hom., cov: 34)

Exomes 𝑓: 0.47 ( 162403 hom. )

Consequence

RECQL4
NM_004260.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.100

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

Baller-Gerold syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
Rothmund-Thomson syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Rothmund-Thomson syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
osteosarcoma
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
rapadilino syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

RECQL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-144514540-G-A is Benign according to our data. Variant chr8-144514540-G-A is described in ClinVar as Benign. ClinVar VariationId is 94886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RECQL4	NM_004260.4	MANE Select	c.1621-15C>T	intron	N/A	NP_004251.4
RECQL4	NM_001413019.1		c.1621-15C>T	intron	N/A	NP_001399948.1
RECQL4	NM_001413036.1		c.1621-15C>T	intron	N/A	NP_001399965.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.1621-15C>T	intron	N/A	ENSP00000482313.2
RECQL4	ENST00000621189.4	TSL:1	c.550-15C>T	intron	N/A	ENSP00000483145.1
RECQL4	ENST00000532846.2	TSL:5	c.475-15C>T	intron	N/A	ENSP00000476551.1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58849

AN:

152050

Hom.:

13348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.579

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.422

GnomAD2 exomes

AF:

0.477

AC:

114486

AN:

240224

AF XY:

0.482

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.560

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.472

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.468

AC:

680427

AN:

1455178

Hom.:

162403

Cov.:

AF XY:

0.472

AC XY:

341259

AN XY:

723420

show subpopulations

African (AFR)

AF:

0.120

AC:

4004

AN:

33396

American (AMR)

AF:

0.549

AC:

24241

AN:

44158

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

11266

AN:

25922

East Asian (EAS)

AF:

0.417

AC:

16514

AN:

39614

South Asian (SAS)

AF:

0.564

AC:

48253

AN:

85622

European-Finnish (FIN)

AF:

0.497

AC:

25522

AN:

51314

Middle Eastern (MID)

AF:

0.358

AC:

2056

AN:

5748

European-Non Finnish (NFE)

AF:

0.470

AC:

521344

AN:

1109230

Other (OTH)

AF:

0.452

AC:

27227

AN:

60174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

19862

39724

59587

79449

99311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15362

30724

46086

61448

76810

<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

AF:

0.387

AC:

58860

AN:

152168

Hom.:

13353

Cov.:

AF XY:

0.395

AC XY:

29362

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.136

AC:

5663

AN:

41518

American (AMR)

AF:

0.509

AC:

7781

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1453

AN:

3470

East Asian (EAS)

AF:

0.470

AC:

2430

AN:

5168

South Asian (SAS)

AF:

0.580

AC:

2797

AN:

4826

European-Finnish (FIN)

AF:

0.502

AC:

5330

AN:

10608

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.473

AC:

32146

AN:

67962

Other (OTH)

AF:

0.421

AC:

890

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1739

3478

5218

6957

8696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.413

Hom.:

5808

Bravo

AF:

0.374

Asia WGS

AF:

0.533

AC:

1852

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 08, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Rapadilino syndrome

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Baller-Gerold syndrome

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.55

(source)

DANN

Benign

0.74

PhyloP100

-0.10

PromoterAI

0.027

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over