8-144515235-C-T

Variant names:

• chr8-144515235-C-T
• rs145615931
• NM_004260.4:c.1398G>A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004260.4(RECQL4):​c.1398G>A​(p.Pro466Pro) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P466P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00081 (5 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -5.87

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 -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 rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.1398G>A	p.Pro466Pro	synonymous_variant	Exon 8 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1398G>A	p.Pro466Pro	synonymous_variant	Exon 8 of 21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.327G>A	p.Pro109Pro	synonymous_variant	Exon 7 of 20	1		ENSP00000483145.1
RECQL4	ENST00000532846.2	c.282G>A	p.Pro94Pro	synonymous_variant	Exon 4 of 9	5		ENSP00000476551.1
RECQL4	ENST00000688394.1	n.421G>A		non_coding_transcript_exon_variant	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 178 AN: 152214 Hom.: 1 Cov.: 34

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.: 1 AF XY: 0.00134 AC XY: 152 AN XY: 113278

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.: 5 Cov.: 33 AF XY: 0.000881 AC XY: 627 AN XY: 712078

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.: 1 Cov.: 34 AF XY: 0.00136 AC XY: 101 AN XY: 74492

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.: 0

Bravo AF: 0.000540

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Dec 06, 2021

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Oct 02, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RECQL4: BP4, BP7 -

Hereditary cancer-predisposing syndrome Benign:1

Oct 07, 2021

Sema4, Sema4

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Baller-Gerold syndrome Benign:1

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs145615931; hg19: chr8-145740619;