chr8-144515758-T-A

Position:

• chr8-144515758-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004260.4(RECQL4):​c.1258+6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,611,922 control chromosomes in the GnomAD database, including 814 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (51 hom., cov: 34)
  • Exomes 𝑓: 0.030 (763 hom.)
• Consequence: RECQL4 NM_004260.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.371

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 8-144515758-T-A is Benign according to our data. Variant chr8-144515758-T-A is described in ClinVar as [Benign]. Clinvar id is 259257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144515758-T-A is described in Lovd as [Benign]. Variant chr8-144515758-T-A is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.1258+6A>T		splice_region_variant, intron_variant		ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1258+6A>T		splice_region_variant, intron_variant		1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.187+6A>T		splice_region_variant, intron_variant		1		ENSP00000483145.1
RECQL4	ENST00000532846.2	c.142+6A>T		splice_region_variant, intron_variant		5		ENSP00000476551.1
RECQL4	ENST00000688394.1	n.-20A>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3420 AN: 152136 Hom.: 51 Cov.: 34

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00725

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0377

GnomAD3 exomes AF: 0.0242 AC: 5958 AN: 246064 Hom.: 108 AF XY: 0.0249 AC XY: 3343 AN XY: 134110

Gnomad AFR exome AF: 0.00564

Gnomad AMR exome AF: 0.0202

Gnomad ASJ exome AF: 0.0547

Gnomad EAS exome AF: 0.0000558

Gnomad SAS exome AF: 0.0142

Gnomad FIN exome AF: 0.00862

Gnomad NFE exome AF: 0.0345

Gnomad OTH exome AF: 0.0319

GnomAD4 exome AF: 0.0296 AC: 43153 AN: 1459668 Hom.: 763 Cov.: 65 AF XY: 0.0294 AC XY: 21375 AN XY: 726006

Gnomad4 AFR exome AF: 0.00822

Gnomad4 AMR exome AF: 0.0202

Gnomad4 ASJ exome AF: 0.0578

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0148

Gnomad4 FIN exome AF: 0.00997

Gnomad4 NFE exome AF: 0.0325

Gnomad4 OTH exome AF: 0.0322

GnomAD4 genome AF: 0.0224 AC: 3416 AN: 152254 Hom.: 51 Cov.: 34 AF XY: 0.0204 AC XY: 1520 AN XY: 74442

Gnomad4 AFR AF: 0.00609

Gnomad4 AMR AF: 0.0283

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00725

Gnomad4 NFE AF: 0.0323

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0310 Hom.: 28

Bravo AF: 0.0240

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0387

EpiControl AF: 0.0392

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 23, 2019	This variant is associated with the following publications: (PMID: 27247962) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.1
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs34437789; hg19: chr8-145741142; COSMIC: COSV52882091; COSMIC: COSV52882091;