rs34700133

chr8-144516228-G-Achr8-144516228-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004260.4(RECQL4):c.891C>T(p.Asp297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,613,116 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.414

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-144516228-G-A is Benign according to our data. Variant chr8-144516228-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 94899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.414 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00208 (317/152306) while in subpopulation AFR AF= 0.0072 (299/41556). AF 95% confidence interval is 0.00652. There are 1 homozygotes in gnomad4. There are 152 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4	c.891C>T	p.Asp297=	synonymous_variant	5/21	ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6	c.891C>T	p.Asp297=	synonymous_variant	5/21	1	NM_004260.4	P1
RECQL4	ENST00000621189.4	c.-181C>T		5_prime_UTR_variant	4/20	1
RECQL4	ENST00000524998.1	c.414C>T	p.Asp138=	synonymous_variant	3/4	3
RECQL4	ENST00000534538.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 319 AN: 152188 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.00726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000670 AC: 166 AN: 247638 Hom.: 2 AF XY: 0.000556 AC XY: 75 AN XY: 134852

Gnomad AFR exome AF: 0.00849

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000668

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000447

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000229 AC: 334 AN: 1460810 Hom.: 2 Cov.: 66 AF XY: 0.000223 AC XY: 162 AN XY: 726666

Gnomad4 AFR exome AF: 0.00681

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.000464

GnomAD4 genome AF: 0.00208 AC: 317 AN: 152306 Hom.: 1 Cov.: 34 AF XY: 0.00204 AC XY: 152 AN XY: 74480

Gnomad4 AFR AF: 0.00720

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00115 Hom.: 0

Bravo AF: 0.00229

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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)	Jul 26, 2013	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 18, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	RECQL4: BP4, BP7, BS2 -

Baller-Gerold syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, criteria provided, single submitter

curation

Sema4, Sema4

May 29, 2021

- -

RECQL4-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.52
Dann	Benign	0.75
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.1

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: rs34700133; hg19: chr8-145741612;