rs558061753

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.2059-8_2059-6delCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000715 in 1,545,812 control chromosomes in the GnomAD database, including 6 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 5 hom. )

Consequence

RECQL4
NM_004260.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.06

Publications

0 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:

ENSG00000265393 (HGNC:):

ENSG00000265393 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 8-144513717-TGAG-T is Benign according to our data. Variant chr8-144513717-TGAG-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414231.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 = 0.00268 (402/150218) while in subpopulation AFR AF = 0.00854 (348/40772). AF 95% confidence interval is 0.0078. There are 1 homozygotes in GnomAd4. There are 200 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.2059-8_2059-6delCTC		splice_region_variant, intron_variant	Intron 12 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.2059-8_2059-6delCTC		splice_region_variant, intron_variant	Intron 12 of 20	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

404

AN:

150098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00861

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000355

Gnomad OTH

AF:

0.00441

GnomAD2 exomes

AF:

0.000850

AC:

130

AN:

152926

AF XY:

0.000654

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.000574

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000322

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000504

AC:

703

AN:

1395594

Hom.:

AF XY:

0.000500

AC XY:

344

AN XY:

688220

show subpopulations

African (AFR)

AF:

0.00994

AC:

313

AN:

31498

American (AMR)

AF:

0.000702

AC:

AN:

35602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25120

East Asian (EAS)

AF:

0.00

AC:

AN:

35594

South Asian (SAS)

AF:

0.0000253

AC:

AN:

79208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47768

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.000268

AC:

289

AN:

1077306

Other (OTH)

AF:

0.00118

AC:

AN:

57816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00268

AC:

402

AN:

150218

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

200

AN XY:

73246

show subpopulations

African (AFR)

AF:

0.00854

AC:

348

AN:

40772

American (AMR)

AF:

0.00133

AC:

AN:

15016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5112

South Asian (SAS)

AF:

0.00

AC:

AN:

4714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10272

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000355

AC:

AN:

67614

Other (OTH)

AF:

0.00436

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00173

Hom.:

Bravo

AF:

0.00328

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

May 18, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Sep 10, 2020

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

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

PhyloP100

2.1

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over