Genetic Variant RECQL4:c.355-8C>T (chr8-144516772-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004260.4(RECQL4):c.355-8C>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 0.00053 in 1,517,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 splice_region, intron

Scores

Splicing: ADA: 0.00003571

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.384

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-144516772-G-A is Benign according to our data. Variant chr8-144516772-G-A is described in ClinVar as Benign. ClinVar VariationId is 414238.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.355-8C>T		splice_region_variant, intron_variant	Intron 4 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.355-8C>T		splice_region_variant, intron_variant	Intron 4 of 20	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000513

AC:

AN:

169498

AF XY:

0.000708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000966

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000778

Gnomad NFE exome

AF:

0.000867

Gnomad OTH exome

AF:

0.000510

GnomAD4 exome

AF:

0.000546

AC:

746

AN:

1365368

Hom.:

Cov.:

AF XY:

0.000593

AC XY:

397

AN XY:

669420

show subpopulations

African (AFR)

AF:

0.0000661

AC:

AN:

30244

American (AMR)

AF:

0.000172

AC:

AN:

28998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19900

East Asian (EAS)

AF:

0.00

AC:

AN:

38976

South Asian (SAS)

AF:

0.00

AC:

AN:

69554

European-Finnish (FIN)

AF:

0.000871

AC:

AN:

47058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5314

European-Non Finnish (NFE)

AF:

0.000629

AC:

672

AN:

1069082

Other (OTH)

AF:

0.000462

AC:

AN:

56242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

125

166

208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<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:

0.000388

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41458

American (AMR)

AF:

0.000196

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

68032

Other (OTH)

AF:

0.000478

AC:

AN:

2090

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:

0.000273

Hom.:

Bravo

AF:

0.000302

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Baller-Gerold syndrome

Benign:1

Jan 20, 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

-0.90

CADD

Benign

0.53

(source)

DANN

Benign

0.47

PhyloP100

-0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over