8-144513212-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_004260.4(RECQL4):c.2463+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000356 in 1,507,762 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 splice_region, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.856

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: 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:

ENSG00000265393 (HGNC:):

ENSG00000265393 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-144513212-G-A is Benign according to our data. Variant chr8-144513212-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 239730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00215 (256/119006) while in subpopulation AFR AF = 0.00784 (244/31142). AF 95% confidence interval is 0.00703. There are 1 homozygotes in GnomAd4. There are 135 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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+6C>T	splice_region intron	N/A	NP_004251.4	O94761
RECQL4	NM_001413019.1		c.2463+6C>T	splice_region intron	N/A	NP_001399948.1
RECQL4	NM_001413036.1		c.2463+6C>T	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+6C>T	splice_region intron	N/A	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4	TSL:1	c.1392+6C>T	splice_region intron	N/A	ENSP00000483145.1	A0A087X072
RECQL4	ENST00000971710.1		c.2370+6C>T	splice_region intron	N/A	ENSP00000641769.1

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

255

AN:

118982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00782

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000834

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000541

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000718

AC:

AN:

119836

AF XY:

0.000526

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.000302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000202

AC:

281

AN:

1388756

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

126

AN XY:

686406

show subpopulations

African (AFR)

AF:

0.00706

AC:

227

AN:

32156

American (AMR)

AF:

0.000471

AC:

AN:

42506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24158

East Asian (EAS)

AF:

0.0000260

AC:

AN:

38492

South Asian (SAS)

AF:

0.0000247

AC:

AN:

81040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36342

Middle Eastern (MID)

AF:

0.000219

AC:

AN:

4570

European-Non Finnish (NFE)

AF:

0.00000933

AC:

AN:

1071704

Other (OTH)

AF:

0.000346

AC:

AN:

57788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00215

AC:

256

AN:

119006

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

135

AN XY:

57178

show subpopulations

African (AFR)

AF:

0.00784

AC:

244

AN:

31142

American (AMR)

AF:

0.000833

AC:

AN:

12004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2900

East Asian (EAS)

AF:

0.00

AC:

AN:

4182

South Asian (SAS)

AF:

0.000544

AC:

AN:

3678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

54860

Other (OTH)

AF:

0.00

AC:

AN:

1628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

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:

0.00144

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Baller-Gerold syndrome (1)

Hereditary cancer-predisposing syndrome (1)

not specified (1)

Rapadilino syndrome (1)

RECQL4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

(source)

DANN

Benign

0.89

PhyloP100

-0.86

PromoterAI

-0.0062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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