Variant 8-144515235-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004260.4(RECQL4):c.1398G>A(p.Pro466=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000846 in 1,588,058 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00081 ( 5 hom. )

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -5.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 8-144515235-C-T is Benign according to our data. Variant chr8-144515235-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144515235-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-5.87 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4 linkuse as main transcript	c.1398G>A	p.Pro466=	synonymous_variant	8/21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RECQL4	ENST00000617875.6 linkuse as main transcript	c.1398G>A	p.Pro466=	synonymous_variant	8/21	1	NM_004260.4	ENSP00000482313	P1
RECQL4	ENST00000621189.4 linkuse as main transcript	c.327G>A	p.Pro109=	synonymous_variant	7/20	1		ENSP00000483145
RECQL4	ENST00000532846.2 linkuse as main transcript	c.285G>A	p.Pro95=	synonymous_variant	4/9	5		ENSP00000476551
RECQL4	ENST00000688394.1 linkuse as main transcript	n.421G>A		non_coding_transcript_exon_variant	2/4

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00611

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00120

AC:

251

AN:

208844

Hom.:

AF XY:

0.00134

AC XY:

152

AN XY:

113278

show subpopulations

Gnomad AFR exome

AF:

0.0000837

Gnomad AMR exome

AF:

0.000200

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000875

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00497

Gnomad NFE exome

AF:

0.000860

Gnomad OTH exome

AF:

0.000939

GnomAD4 exome

AF:

0.000812

AC:

1166

AN:

1435726

Hom.:

Cov.:

AF XY:

0.000881

AC XY:

627

AN XY:

712078

show subpopulations

Gnomad4 AFR exome

AF:

0.0000610

Gnomad4 AMR exome

AF:

0.000222

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.000550

Gnomad4 SAS exome

AF:

0.00227

Gnomad4 FIN exome

AF:

0.00474

Gnomad4 NFE exome

AF:

0.000610

Gnomad4 OTH exome

AF:

0.000572

GnomAD4 genome

AF:

0.00116

AC:

177

AN:

152332

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00611

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.000540

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 06, 2021

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

RECQL4: BP4, BP7 -

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, criteria provided, single submitter

curation

Sema4, Sema4

Oct 07, 2021

- -

Baller-Gerold syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.20

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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