8-144517466-T-C

Position:

chr8-144517466-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004260.4(RECQL4):c.161A>G(p.Gln54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,596,194 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 12 hom., cov: 35)

Exomes 𝑓: 0.0032 ( 31 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: -0.370

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032030642).

BP6

Variant 8-144517466-T-C is Benign according to our data. Variant chr8-144517466-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 135157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517466-T-C is described in Lovd as [Benign]. Variant chr8-144517466-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00973 (1481/152230) while in subpopulation AFR AF= 0.0277 (1151/41542). AF 95% confidence interval is 0.0264. There are 12 homozygotes in gnomad4. There are 700 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.161A>G	p.Gln54Arg	missense_variant	3/21	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6 link	c.161A>G	p.Gln54Arg	missense_variant	3/21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.00963

AC:

1465

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0274

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00365

AC:

776

AN:

212724

Hom.:

AF XY:

0.00334

AC XY:

395

AN XY:

118178

show subpopulations

Gnomad AFR exome

AF:

0.0247

Gnomad AMR exome

AF:

0.00561

Gnomad ASJ exome

AF:

0.00614

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000528

Gnomad FIN exome

AF:

0.000138

Gnomad NFE exome

AF:

0.00216

Gnomad OTH exome

AF:

0.00478

GnomAD4 exome

AF:

0.00325

AC:

4692

AN:

1443964

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

2208

AN XY:

717566

show subpopulations

Gnomad4 AFR exome

AF:

0.0275

Gnomad4 AMR exome

AF:

0.00589

Gnomad4 ASJ exome

AF:

0.00715

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000461

Gnomad4 FIN exome

AF:

0.000202

Gnomad4 NFE exome

AF:

0.00266

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.00973

AC:

1481

AN:

152230

Hom.:

Cov.:

AF XY:

0.00940

AC XY:

700

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.00712

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00234

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00352

Hom.:

Bravo

AF:

0.0111

ESP6500AA

AF:

0.0135

AC:

ESP6500EA

AF:

0.00135

AC:

ExAC

AF:

0.00347

AC:

405

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4Other:1

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 28, 2016	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 05, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -

Rothmund-Thomson syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Baller-Gerold syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

curation

Sema4, Sema4

Oct 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Benign

1.6

DANN

Benign

0.62

DEOGEN2

Benign

0.031

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0032

PrimateAI

Uncertain

0.63

Sift4G

Benign

0.19

Polyphen

0.0010

Vest4

0.054

MVP

0.76

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.094

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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