chr8-144515746-C-T

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.1258+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,610,022 control chromosomes in the GnomAD database, including 175,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13513 hom., cov: 34)

Exomes 𝑓: 0.47 ( 161818 hom. )

Consequence

RECQL4
NM_004260.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.296

Publications

24 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 (BayesDel_noAF=-0.78).

BP6

Variant 8-144515746-C-T is Benign according to our data. Variant chr8-144515746-C-T is described in ClinVar as Benign. ClinVar VariationId is 94884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 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	Effect	Exon Rank	Protein	UniProt
RECQL4	NM_004260.4	MANE Select	c.1258+18G>A	intron	N/A	NP_004251.4	O94761
RECQL4	NM_001413019.1		c.1258+18G>A	intron	N/A	NP_001399948.1
RECQL4	NM_001413036.1		c.1258+18G>A	intron	N/A	NP_001399965.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.1258+18G>A	intron	N/A	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4	TSL:1	c.187+18G>A	intron	N/A	ENSP00000483145.1	A0A087X072
RECQL4	ENST00000971710.1		c.1165+18G>A	intron	N/A	ENSP00000641769.1

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60246

AN:

152020

Hom.:

13508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.581

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.427

GnomAD2 exomes

AF:

0.475

AC:

115771

AN:

243622

AF XY:

0.480

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.559

Gnomad ASJ exome

AF:

0.445

Gnomad EAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.492

Gnomad NFE exome

AF:

0.469

Gnomad OTH exome

AF:

0.464

GnomAD4 exome

AF:

0.467

AC:

680732

AN:

1457884

Hom.:

161818

Cov.:

AF XY:

0.471

AC XY:

341381

AN XY:

724960

show subpopulations

African (AFR)

AF:

0.158

AC:

5302

AN:

33452

American (AMR)

AF:

0.548

AC:

24316

AN:

44334

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

11319

AN:

26046

East Asian (EAS)

AF:

0.416

AC:

16479

AN:

39596

South Asian (SAS)

AF:

0.563

AC:

48327

AN:

85882

European-Finnish (FIN)

AF:

0.493

AC:

25621

AN:

51980

Middle Eastern (MID)

AF:

0.357

AC:

2057

AN:

5758

European-Non Finnish (NFE)

AF:

0.468

AC:

519965

AN:

1110584

Other (OTH)

AF:

0.454

AC:

27346

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

20256

40512

60769

81025

101281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15356

30712

46068

61424

76780

<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:

0.396

AC:

60267

AN:

152138

Hom.:

13513

Cov.:

AF XY:

0.403

AC XY:

29989

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.174

AC:

7217

AN:

41540

American (AMR)

AF:

0.510

AC:

7810

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1454

AN:

3472

East Asian (EAS)

AF:

0.469

AC:

2420

AN:

5162

South Asian (SAS)

AF:

0.581

AC:

2804

AN:

4826

European-Finnish (FIN)

AF:

0.500

AC:

5294

AN:

10578

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.471

AC:

31996

AN:

67932

Other (OTH)

AF:

0.427

AC:

903

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1770

3540

5309

7079

8849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.455

Hom.:

26392

Bravo

AF:

0.385

Asia WGS

AF:

0.540

AC:

1877

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Baller-Gerold syndrome (2)

not provided (2)

not specified (2)

Rapadilino syndrome (2)

Rothmund-Thomson syndrome type 2 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.4

(source)

DANN

Benign

0.64

PhyloP100

0.30

PromoterAI

0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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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