8-144516318-C-G

Variant names:

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.801G>C(p.Glu267Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,608,224 control chromosomes in the GnomAD database, including 137,225 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 13793 hom., cov: 34)

Exomes 𝑓: 0.41 ( 123432 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: -1.07

Publications

41 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.5492116E-5).

BP6

Variant 8-144516318-C-G is Benign according to our data. Variant chr8-144516318-C-G is described in ClinVar as Benign. ClinVar VariationId is 94898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 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	UniProt
RECQL4	NM_004260.4	MANE Select	c.801G>C	p.Glu267Asp	missense	Exon 5 of 21	NP_004251.4	O94761
RECQL4	NM_001413019.1		c.801G>C	p.Glu267Asp	missense	Exon 5 of 20	NP_001399948.1
RECQL4	NM_001413036.1		c.801G>C	p.Glu267Asp	missense	Exon 5 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.801G>C	p.Glu267Asp	missense	Exon 5 of 21	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4	TSL:1	c.-271G>C		5_prime_UTR	Exon 4 of 20	ENSP00000483145.1	A0A087X072
RECQL4	ENST00000971710.1		c.801G>C	p.Glu267Asp	missense	Exon 5 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64160

AN:

151954

Hom.:

13773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.435

GnomAD2 exomes

AF:

0.437

AC:

105355

AN:

240852

AF XY:

0.435

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.534

Gnomad ASJ exome

AF:

0.385

Gnomad EAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.409

AC:

596009

AN:

1456152

Hom.:

123432

Cov.:

AF XY:

0.412

AC XY:

298362

AN XY:

724102

show subpopulations

African (AFR)

AF:

0.428

AC:

14321

AN:

33456

American (AMR)

AF:

0.524

AC:

23167

AN:

44216

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

9820

AN:

26062

East Asian (EAS)

AF:

0.395

AC:

15642

AN:

39616

South Asian (SAS)

AF:

0.497

AC:

42716

AN:

85984

European-Finnish (FIN)

AF:

0.417

AC:

21051

AN:

50484

Middle Eastern (MID)

AF:

0.311

AC:

1793

AN:

5764

European-Non Finnish (NFE)

AF:

0.399

AC:

442864

AN:

1110346

Other (OTH)

AF:

0.409

AC:

24635

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

22277

44553

66830

89106

111383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13826

27652

41478

55304

69130

<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:

0.422

AC:

64221

AN:

152072

Hom.:

13793

Cov.:

AF XY:

0.427

AC XY:

31713

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.426

AC:

17667

AN:

41494

American (AMR)

AF:

0.483

AC:

7376

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1267

AN:

3472

East Asian (EAS)

AF:

0.453

AC:

2339

AN:

5160

South Asian (SAS)

AF:

0.512

AC:

2468

AN:

4822

European-Finnish (FIN)

AF:

0.424

AC:

4483

AN:

10568

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.403

AC:

27419

AN:

67960

Other (OTH)

AF:

0.434

AC:

916

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1970

3940

5910

7880

9850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.406

Hom.:

2917

Bravo

AF:

0.427

TwinsUK

AF:

0.395

AC:

1466

ALSPAC

AF:

0.398

AC:

1534

ESP6500AA

AF:

0.410

AC:

1614

ESP6500EA

AF:

0.383

AC:

3184

ExAC

AF:

0.426

AC:

51219

Asia WGS

AF:

0.515

AC:

1790

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Baller-Gerold syndrome (2)

not provided (2)

Rapadilino syndrome (2)

Rothmund-Thomson syndrome type 2 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.28

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.031

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.38

MetaRNN

Benign

0.000085

PhyloP100

-1.1

PrimateAI

Benign

0.28

Sift4G

Benign

0.31

Polyphen

0.0020

Vest4

0.067

GERP RS

-3.0

PromoterAI

0.051

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.034

gMVP

0.12

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over