chr8-144513202-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004260.4(RECQL4):c.2463+16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,534,620 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0076 ( 79 hom. )

Consequence

RECQL4
NM_004260.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.44

Publications

1 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 8-144513202-G-T is Benign according to our data. Variant chr8-144513202-G-T is described in ClinVar as Benign. ClinVar VariationId is 445471.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00707 (1070/151316) while in subpopulation AMR AF = 0.0114 (174/15226). AF 95% confidence interval is 0.01. There are 9 homozygotes in GnomAd4. There are 566 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.2463+16C>A		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+16C>A	intron_variant	Intron 14 of 20	1	NM_004260.4	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4 link	c.1392+16C>A	intron_variant	Intron 13 of 19	1		ENSP00000483145.1	A0A087X072
RECQL4	ENST00000534626.6 link	c.634-64C>A	intron_variant	Intron 5 of 7	5		ENSP00000477457.1	V9GZ64
ENSG00000265393	ENST00000580385.1 link	n.271+365G>T	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00708

AC:

1070

AN:

151216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00348

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000626

Gnomad FIN

AF:

0.0214

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00854

Gnomad OTH

AF:

0.00725

GnomAD2 exomes

AF:

0.0131

AC:

1477

AN:

112448

AF XY:

0.0131

show subpopulations

Gnomad AFR exome

AF:

0.00241

Gnomad AMR exome

AF:

0.0125

Gnomad ASJ exome

AF:

0.00971

Gnomad EAS exome

AF:

0.00117

Gnomad FIN exome

AF:

0.0450

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0177

GnomAD4 exome

AF:

0.00763

AC:

10556

AN:

1383304

Hom.:

Cov.:

AF XY:

0.00753

AC XY:

5142

AN XY:

682504

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

32598

American (AMR)

AF:

0.00854

AC:

357

AN:

41812

Ashkenazi Jewish (ASJ)

AF:

0.00438

AC:

103

AN:

23490

East Asian (EAS)

AF:

0.000239

AC:

AN:

37708

South Asian (SAS)

AF:

0.00113

AC:

AN:

77752

European-Finnish (FIN)

AF:

0.0237

AC:

834

AN:

35256

Middle Eastern (MID)

AF:

0.00198

AC:

AN:

5044

European-Non Finnish (NFE)

AF:

0.00814

AC:

8731

AN:

1072314

Other (OTH)

AF:

0.00666

AC:

382

AN:

57330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.551

Heterozygous variant carriers

573

1146

1720

2293

2866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.00707

AC:

1070

AN:

151316

Hom.:

Cov.:

AF XY:

0.00766

AC XY:

566

AN XY:

73904

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41426

American (AMR)

AF:

0.0114

AC:

174

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00348

AC:

AN:

3446

East Asian (EAS)

AF:

0.000195

AC:

AN:

5134

South Asian (SAS)

AF:

0.000626

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.0214

AC:

224

AN:

10478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00855

AC:

577

AN:

67520

Other (OTH)

AF:

0.00718

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: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

-0.88

CADD

Benign

0.064

(source)

DANN

Benign

0.57

PhyloP100

-1.4

PromoterAI

0.010

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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