rs750392035

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_004260.4(RECQL4):c.2463+7_2463+8delAC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RECQL4
NM_004260.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

Publications

0 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
osteosarcoma
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
rapadilino syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RECQL4 links:

ENSG00000265393 (HGNC:):

ENSG00000265393 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004260.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 8-144513209-GGT-G is Benign according to our data. Variant chr8-144513209-GGT-G is described in ClinVar as Likely_benign. ClinVar VariationId is 239731.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2463+7_2463+8delAC	splice_region intron	N/A	NP_004251.4	O94761
RECQL4	NM_001413019.1		c.2463+7_2463+8delAC	splice_region intron	N/A	NP_001399948.1
RECQL4	NM_001413036.1		c.2463+7_2463+8delAC	splice_region 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.2463+7_2463+8delAC	splice_region intron	N/A	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4	TSL:1	c.1392+7_1392+8delAC	splice_region intron	N/A	ENSP00000483145.1	A0A087X072
RECQL4	ENST00000971710.1		c.2370+7_2370+8delAC	splice_region intron	N/A	ENSP00000641769.1

Frequencies

GnomAD3 genomes

AF:

0.00207

AC:

304

AN:

146940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000988

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.00299

Gnomad ASJ

AF:

0.00176

Gnomad EAS

AF:

0.00202

Gnomad SAS

AF:

0.00402

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00502

GnomAD2 exomes

AF:

0.00571

AC:

971

AN:

169988

AF XY:

0.00656

show subpopulations

Gnomad AFR exome

AF:

0.00371

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.00260

Gnomad FIN exome

AF:

0.00971

Gnomad NFE exome

AF:

0.00598

Gnomad OTH exome

AF:

0.00286

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00122

AC:

1670

AN:

1371710

Hom.:

AF XY:

0.00153

AC XY:

1037

AN XY:

676684

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00108

AC:

AN:

32354

American (AMR)

AF:

0.00494

AC:

205

AN:

41526

Ashkenazi Jewish (ASJ)

AF:

0.00296

AC:

AN:

23628

East Asian (EAS)

AF:

0.00212

AC:

AN:

38192

South Asian (SAS)

AF:

0.00528

AC:

414

AN:

78390

European-Finnish (FIN)

AF:

0.00210

AC:

AN:

35702

Middle Eastern (MID)

AF:

0.00205

AC:

AN:

4888

European-Non Finnish (NFE)

AF:

0.000665

AC:

705

AN:

1059798

Other (OTH)

AF:

0.00131

AC:

AN:

57232

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.377

Heterozygous variant carriers

155

232

310

387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00207

AC:

305

AN:

147020

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

174

AN XY:

71434

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000986

AC:

AN:

40580

American (AMR)

AF:

0.00299

AC:

AN:

14736

Ashkenazi Jewish (ASJ)

AF:

0.00176

AC:

AN:

3410

East Asian (EAS)

AF:

0.00203

AC:

AN:

4934

South Asian (SAS)

AF:

0.00403

AC:

AN:

4466

European-Finnish (FIN)

AF:

0.00235

AC:

AN:

9800

Middle Eastern (MID)

AF:

0.00355

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00231

AC:

152

AN:

65894

Other (OTH)

AF:

0.00497

AC:

AN:

2014

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.301

Heterozygous variant carriers

105

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:

0.00322

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Baller-Gerold syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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