rs756627

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3393+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 0.459 in 1,609,516 control chromosomes in the GnomAD database, including 175,591 homozygotes. 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 0.39 ( 13393 hom., cov: 35)

Exomes 𝑓: 0.47 ( 162198 hom. )

Consequence

RECQL4
NM_004260.4 splice_region, intron

Scores

Splicing: ADA: 0.00003801

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.00

Publications

33 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 (MetaRNN=2.8563938E-5).

BP6

Variant 8-144511903-G-A is Benign according to our data. Variant chr8-144511903-G-A is described in ClinVar as Benign. ClinVar VariationId is 94894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 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	HGVSp	Effect	Exon Rank	Protein
RECQL4	NM_004260.4	MANE Select	c.3393+8C>T		splice_region intron	N/A	NP_004251.4
RECQL4	NM_001413036.1		c.3401C>T	p.Ala1134Val	missense splice_region	Exon 19 of 21	NP_001399965.1
RECQL4	NM_001413019.1		c.3468+8C>T		splice_region intron	N/A	NP_001399948.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.3393+8C>T		splice_region intron	N/A	ENSP00000482313.2
RECQL4	ENST00000621189.4	TSL:1	c.2322+8C>T		splice_region intron	N/A	ENSP00000483145.1
RECQL4	ENST00000531875.2	TSL:5	c.647C>T	p.Ala216Val	missense splice_region	Exon 4 of 6	ENSP00000477910.1

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58955

AN:

152096

Hom.:

13389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.420

GnomAD2 exomes

AF:

0.476

AC:

116530

AN:

244932

AF XY:

0.482

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.560

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.493

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.470

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.467

AC:

680494

AN:

1457302

Hom.:

162198

Cov.:

AF XY:

0.471

AC XY:

341695

AN XY:

724980

show subpopulations

African (AFR)

AF:

0.124

AC:

4148

AN:

33472

American (AMR)

AF:

0.549

AC:

24514

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

11465

AN:

26120

East Asian (EAS)

AF:

0.443

AC:

17568

AN:

39684

South Asian (SAS)

AF:

0.565

AC:

48748

AN:

86234

European-Finnish (FIN)

AF:

0.494

AC:

24633

AN:

49912

Middle Eastern (MID)

AF:

0.358

AC:

2062

AN:

5762

European-Non Finnish (NFE)

AF:

0.468

AC:

520064

AN:

1111190

Other (OTH)

AF:

0.453

AC:

27292

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

20245

40489

60734

80978

101223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15352

30704

46056

61408

76760

<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:

58965

AN:

152214

Hom.:

13393

Cov.:

AF XY:

0.395

AC XY:

29397

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.139

AC:

5767

AN:

41556

American (AMR)

AF:

0.507

AC:

7752

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1464

AN:

3472

East Asian (EAS)

AF:

0.493

AC:

2550

AN:

5172

South Asian (SAS)

AF:

0.587

AC:

2837

AN:

4830

European-Finnish (FIN)

AF:

0.500

AC:

5297

AN:

10604

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.471

AC:

32049

AN:

67976

Other (OTH)

AF:

0.418

AC:

885

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1739

3478

5216

6955

8694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.421

Hom.:

33435

Bravo

AF:

0.375

TwinsUK

AF:

0.457

AC:

1696

ALSPAC

AF:

0.469

AC:

1806

ESP6500AA

AF:

0.139

AC:

598

ESP6500EA

AF:

0.457

AC:

3883

ExAC

AF:

0.463

AC:

55704

Asia WGS

AF:

0.529

AC:

1838

AN:

3478

EpiCase

AF:

0.470

EpiControl

AF:

0.471

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Baller-Gerold syndrome (2)

not provided (2)

Rapadilino syndrome (1)

Rothmund-Thomson syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.0

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0024

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.28

MetaRNN

Benign

0.000029

PhyloP100

1.0

Sift4G

Benign

0.30

GERP RS

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.10

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over