8-144513211-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_004260.4(RECQL4):c.2463+7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RECQL4
NM_004260.4 splice_region, intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 8-144513211-T-G is Benign according to our data. Variant chr8-144513211-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 239732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

10214

AN:

78408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.0998

Gnomad SAS

AF:

0.0467

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.151

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.00691

AC:

457

AN:

66174

AF XY:

0.00706

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.00633

Gnomad ASJ exome

AF:

0.00757

Gnomad EAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.00706

Gnomad NFE exome

AF:

0.00617

Gnomad OTH exome

AF:

0.00566

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00210

AC:

1896

AN:

901164

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

992

AN XY:

441074

show subpopulations

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

African (AFR)

AF:

0.00637

AC:

136

AN:

21350

American (AMR)

AF:

0.00505

AC:

130

AN:

25764

Ashkenazi Jewish (ASJ)

AF:

0.00397

AC:

AN:

16126

East Asian (EAS)

AF:

0.00405

AC:

119

AN:

29378

South Asian (SAS)

AF:

0.00383

AC:

156

AN:

40744

European-Finnish (FIN)

AF:

0.00235

AC:

AN:

26366

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

2770

European-Non Finnish (NFE)

AF:

0.00159

AC:

1113

AN:

699632

Other (OTH)

AF:

0.00266

AC:

104

AN:

39034

⚠️ 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: 0.252

Heterozygous variant carriers

285

570

854

1139

1424

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:

0.130

AC:

10219

AN:

78438

Hom.:

Cov.:

AF XY:

0.128

AC XY:

4744

AN XY:

36992

show subpopulations

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

African (AFR)

AF:

0.167

AC:

3227

AN:

19350

American (AMR)

AF:

0.133

AC:

1101

AN:

8288

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

257

AN:

2034

East Asian (EAS)

AF:

0.100

AC:

232

AN:

2318

South Asian (SAS)

AF:

0.0468

AC:

116

AN:

2478

European-Finnish (FIN)

AF:

0.106

AC:

505

AN:

4766

Middle Eastern (MID)

AF:

0.157

AC:

AN:

134

European-Non Finnish (NFE)

AF:

0.121

AC:

4533

AN:

37544

Other (OTH)

AF:

0.125

AC:

133

AN:

1062

⚠️ 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: 0.354

Heterozygous variant carriers

503

1006

1509

2012

2515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

112

224

336

448

560

<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:

0.00786

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Baller-Gerold syndrome

Benign:1

May 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.28

(source)

DANN

Benign

0.55

PhyloP100

-3.1

PromoterAI

0.0026

Neutral

(source)

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over