dbSNP rs760575376: RECQL4:c.2463+7delA (chr8-144513210-GT-G) – ACMG Classification: Likely_benign (-2 pts)

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+7delA 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 Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00081 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RECQL4
NM_004260.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.11

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, 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:

ENSG00000265393 (HGNC:):

ENSG00000265393 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP6

Variant 8-144513210-GT-G is Benign according to our data. Variant chr8-144513210-GT-G is described in ClinVar as Benign. ClinVar VariationId is 239733.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.2463+7delA		splice_region_variant, intron_variant	Intron 14 of 20	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RECQL4	ENST00000617875.6 link	c.2463+7delA	splice_region_variant, intron_variant	Intron 14 of 20	1	NM_004260.4	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4 link	c.1392+7delA	splice_region_variant, intron_variant	Intron 13 of 19	1		ENSP00000483145.1	A0A087X072
RECQL4	ENST00000534626.6 link	c.634-73delA	intron_variant	Intron 5 of 7	5		ENSP00000477457.1	V9GZ64
ENSG00000265393	ENST00000580385.1 link	n.271+374delT	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

303

AN:

125398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00602

Gnomad AMI

AF:

0.00380

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.000999

Gnomad EAS

AF:

0.000722

Gnomad SAS

AF:

0.000527

Gnomad FIN

AF:

0.000619

Gnomad MID

AF:

0.00394

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.00176

GnomAD2 exomes

AF:

0.00639

AC:

773

AN:

120940

AF XY:

0.00755

show subpopulations

Gnomad AFR exome

AF:

0.00718

Gnomad AMR exome

AF:

0.00291

Gnomad ASJ exome

AF:

0.00432

Gnomad EAS exome

AF:

0.00273

Gnomad FIN exome

AF:

0.00949

Gnomad NFE exome

AF:

0.00819

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000813

AC:

1065

AN:

1310156

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

668

AN XY:

641164

show subpopulations

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

African (AFR)

AF:

0.00155

AC:

AN:

30950

American (AMR)

AF:

0.00365

AC:

130

AN:

35600

Ashkenazi Jewish (ASJ)

AF:

0.00252

AC:

AN:

21800

East Asian (EAS)

AF:

0.00113

AC:

AN:

35340

South Asian (SAS)

AF:

0.00282

AC:

188

AN:

66762

European-Finnish (FIN)

AF:

0.00110

AC:

AN:

32790

Middle Eastern (MID)

AF:

0.00142

AC:

AN:

4234

European-Non Finnish (NFE)

AF:

0.000528

AC:

543

AN:

1027956

Other (OTH)

AF:

0.000347

AC:

AN:

54724

⚠️ 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: 0.333

Heterozygous variant carriers

124

187

249

311

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:

0.00242

AC:

303

AN:

125444

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

142

AN XY:

60382

show subpopulations

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

African (AFR)

AF:

0.00603

AC:

213

AN:

35318

American (AMR)

AF:

0.00112

AC:

AN:

12498

Ashkenazi Jewish (ASJ)

AF:

0.000999

AC:

AN:

3002

East Asian (EAS)

AF:

0.000724

AC:

AN:

4144

South Asian (SAS)

AF:

0.000265

AC:

AN:

3774

European-Finnish (FIN)

AF:

0.000619

AC:

AN:

8080

Middle Eastern (MID)

AF:

0.00431

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00102

AC:

AN:

55882

Other (OTH)

AF:

0.00174

AC:

AN:

1724

⚠️ 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: 0.319

Heterozygous variant carriers

106

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:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Baller-Gerold syndrome

Benign:1

Aug 17, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over