8-144511902-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004260.4(RECQL4):c.3393+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,610,494 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 51 hom., cov: 34)

Exomes 𝑓: 0.027 ( 634 hom. )

Consequence

RECQL4
NM_004260.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.998

Publications

5 publications found

Variant links:

COSMIC-nc: COSV56742465

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 -16 ACMG points.

BP6

Variant 8-144511902-T-C is Benign according to our data. Variant chr8-144511902-T-C is described in ClinVar as Benign. ClinVar VariationId is 259260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0203 (3089/152362) while in subpopulation NFE AF = 0.0279 (1895/68026). AF 95% confidence interval is 0.0268. There are 51 homozygotes in GnomAd4. There are 1483 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.3393+9A>G		intron_variant	Intron 19 of 20	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6 link	c.3393+9A>G		intron_variant	Intron 19 of 20	1	NM_004260.4	ENSP00000482313.2

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3089

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00593

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.0770

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0380

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0279

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0231

AC:

5664

AN:

245642

AF XY:

0.0232

show subpopulations

Gnomad AFR exome

AF:

0.00444

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0761

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0377

Gnomad NFE exome

AF:

0.0296

Gnomad OTH exome

AF:

0.0297

GnomAD4 exome

AF:

0.0270

AC:

39370

AN:

1458132

Hom.:

634

Cov.:

AF XY:

0.0267

AC XY:

19373

AN XY:

725394

show subpopulations

African (AFR)

AF:

0.00475

AC:

159

AN:

33472

American (AMR)

AF:

0.0142

AC:

636

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0757

AC:

1977

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39692

South Asian (SAS)

AF:

0.00477

AC:

411

AN:

86246

European-Finnish (FIN)

AF:

0.0371

AC:

1864

AN:

50250

Middle Eastern (MID)

AF:

0.0179

AC:

103

AN:

5766

European-Non Finnish (NFE)

AF:

0.0292

AC:

32437

AN:

1111546

Other (OTH)

AF:

0.0295

AC:

1781

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

2180

4359

6539

8718

10898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1208

2416

3624

4832

6040

<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:

0.0203

AC:

3089

AN:

152362

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1483

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.00592

AC:

246

AN:

41588

American (AMR)

AF:

0.0131

AC:

201

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0770

AC:

267

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00517

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0380

AC:

404

AN:

10624

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0279

AC:

1895

AN:

68026

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

158

316

475

633

791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0247

Hom.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0320

EpiControl

AF:

0.0289

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Baller-Gerold syndrome

Benign:1

Oct 27, 2023

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

-0.84

CADD

Benign

0.19

(source)

DANN

Benign

0.54

PhyloP100

-1.0

Mutation Taster

=24/76

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.35

Position offset: 0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over