Variant chr8-144512253-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004260.4(RECQL4):c.3127T>C(p.Leu1043Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,612,502 control chromosomes in the GnomAD database, including 789,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74151 hom., cov: 37)

Exomes 𝑓: 0.99 ( 715666 hom. )

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.01

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 8-144512253-A-G is Benign according to our data. Variant chr8-144512253-A-G is described in ClinVar as [Benign]. Clinvar id is 167573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512253-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.3127T>C	p.Leu1043Leu	synonymous_variant	18/21	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6 link	c.3127T>C	p.Leu1043Leu	synonymous_variant	18/21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.986

AC:

150063

AN:

152226

Hom.:

74094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.994

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.952

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.989

GnomAD3 exomes

AF:

0.970

AC:

239773

AN:

247306

Hom.:

116726

AF XY:

0.975

AC XY:

131526

AN XY:

134888

show subpopulations

Gnomad AFR exome

AF:

0.995

Gnomad AMR exome

AF:

0.904

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.997

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.981

GnomAD4 exome

AF:

0.989

AC:

1443943

AN:

1460158

Hom.:

715666

Cov.:

AF XY:

0.990

AC XY:

718755

AN XY:

726346

show subpopulations

Gnomad4 AFR exome

AF:

0.996

Gnomad4 AMR exome

AF:

0.909

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

0.732

Gnomad4 SAS exome

AF:

0.998

Gnomad4 FIN exome

AF:

0.996

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.988

GnomAD4 genome

AF:

0.986

AC:

150179

AN:

152344

Hom.:

74151

Cov.:

AF XY:

0.984

AC XY:

73312

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.994

Gnomad4 AMR

AF:

0.952

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

0.787

Gnomad4 SAS

AF:

0.997

Gnomad4 FIN

AF:

0.998

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.989

Alfa

AF:

0.991

Hom.:

67028

Bravo

AF:

0.981

Asia WGS

AF:

0.939

AC:

3266

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Baller-Gerold syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 02, 2012

- -

Rapadilino syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Rothmund-Thomson syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.9

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over