rs373178405

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004260.4(RECQL4):c.1708C>T(p.Arg570Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,600,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R570Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5O:1

Conservation

PhyloP100: 1.34

Publications

4 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, SUPPORTIVE Submitted by: Orphanet, G2P
Rothmund-Thomson syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Rothmund-Thomson syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P
osteosarcoma
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
rapadilino syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RECQL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021208763).

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	UniProt
RECQL4	NM_004260.4	MANE Select	c.1708C>T	p.Arg570Trp	missense	Exon 11 of 21	NP_004251.4	O94761
RECQL4	NM_001413019.1		c.1708C>T	p.Arg570Trp	missense	Exon 11 of 20	NP_001399948.1
RECQL4	NM_001413036.1		c.1708C>T	p.Arg570Trp	missense	Exon 11 of 21	NP_001399965.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.1708C>T	p.Arg570Trp	missense	Exon 11 of 21	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4	TSL:1	c.637C>T	p.Arg213Trp	missense	Exon 10 of 20	ENSP00000483145.1	A0A087X072
RECQL4	ENST00000971710.1		c.1615C>T	p.Arg539Trp	missense	Exon 11 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000343

AC:

AN:

239318

AF XY:

0.000352

show subpopulations

Gnomad AFR exome

AF:

0.0000682

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000486

Gnomad NFE exome

AF:

0.000307

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000541

AC:

783

AN:

1447900

Hom.:

Cov.:

AF XY:

0.000542

AC XY:

389

AN XY:

718234

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33256

American (AMR)

AF:

0.00109

AC:

AN:

44134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25590

East Asian (EAS)

AF:

0.00

AC:

AN:

39410

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85520

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.000626

AC:

691

AN:

1103178

Other (OTH)

AF:

0.000686

AC:

AN:

59780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.000263

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41530

American (AMR)

AF:

0.000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

67962

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000378

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.000274

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Baller-Gerold syndrome (1)

Hereditary cancer-predisposing syndrome (1)

Rothmund-Thomson syndrome type 2 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.15

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.81

M_CAP

Benign

0.0066

MetaRNN

Benign

0.021

PhyloP100

1.3

PrimateAI

Benign

0.22

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.41

MVP

0.74

GERP RS

3.3

PromoterAI

0.0065

Neutral

(source)

Varity_R

0.49

gMVP

0.63

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over