chr8-144517495-T-C

Position:

• chr8-144517495-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004260.4(RECQL4):​c.132A>G​(p.Glu44Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,591,644 control chromosomes in the GnomAD database, including 213,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23183 hom., cov: 35)
  • Exomes 𝑓: 0.51 (189901 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.186

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-144517495-T-C is Benign according to our data. Variant chr8-144517495-T-C is described in ClinVar as [Benign]. Clinvar id is 94885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517495-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.186 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.132A>G	p.Glu44Glu	synonymous_variant	3/21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.132A>G	p.Glu44Glu	synonymous_variant	3/21	1	NM_004260.4	ENSP00000482313.2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83323 AN: 151950 Hom.: 23153 Cov.: 35

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.546

GnomAD3 exomes AF: 0.537 AC: 112047 AN: 208800 Hom.: 30572 AF XY: 0.534 AC XY: 61976 AN XY: 116114

Gnomad AFR exome AF: 0.616

Gnomad AMR exome AF: 0.645

Gnomad ASJ exome AF: 0.479

Gnomad EAS exome AF: 0.486

Gnomad SAS exome AF: 0.603

Gnomad FIN exome AF: 0.481

Gnomad NFE exome AF: 0.493

Gnomad OTH exome AF: 0.509

GnomAD4 exome AF: 0.511 AC: 735776 AN: 1439580 Hom.: 189901 Cov.: 47 AF XY: 0.513 AC XY: 367242 AN XY: 715246

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.443

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.548 AC: 83407 AN: 152064 Hom.: 23183 Cov.: 35 AF XY: 0.554 AC XY: 41184 AN XY: 74330

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.545

Alfa AF: 0.530 Hom.: 8370

Bravo AF: 0.557

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 16, 2016	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 10, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Rothmund-Thomson syndrome type 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

Baller-Gerold syndrome Benign:2

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

Rapadilino syndrome 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	-0.81
CADD	Benign	7.4
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2306386; hg19: chr8-145742879; COSMIC: COSV52877828; COSMIC: COSV52877828;