rs558061753

chr8-144513717-TGAG-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_004260.4(RECQL4):c.2059-8_2059-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000715 in 1,545,812 control chromosomes in the GnomAD database, including 6 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (5 hom.)
• Consequence: RECQL4 NM_004260.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.06

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 8-144513717-TGAG-T is Benign according to our data. Variant chr8-144513717-TGAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 414231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144513717-TGAG-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00268 (402/150218) while in subpopulation AFR AF= 0.00854 (348/40772). AF 95% confidence interval is 0.0078. There are 1 homozygotes in gnomad4. There are 200 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4	c.2059-8_2059-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6	c.2059-8_2059-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004260.4	P1
	ENST00000580385.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 404 AN: 150098 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00861

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000355

Gnomad OTH AF: 0.00441

GnomAD3 exomes AF: 0.000850 AC: 130 AN: 152926 Hom.: 4 AF XY: 0.000654 AC XY: 53 AN XY: 81082

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.000574

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000322

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000504 AC: 703 AN: 1395594 Hom.: 5 AF XY: 0.000500 AC XY: 344 AN XY: 688220

Gnomad4 AFR exome AF: 0.00994

Gnomad4 AMR exome AF: 0.000702

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000253

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000268

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.00268 AC: 402 AN: 150218 Hom.: 1 Cov.: 32 AF XY: 0.00273 AC XY: 200 AN XY: 73246

Gnomad4 AFR AF: 0.00854

Gnomad4 AMR AF: 0.00133

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000355

Gnomad4 OTH AF: 0.00436

Alfa AF: 0.00173 Hom.: 0

Bravo AF: 0.00328

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 18, 2020

- -

Baller-Gerold syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Hereditary cancer-predisposing syndrome Benign:1

Benign, criteria provided, single submitter

curation

Sema4, Sema4

Sep 10, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs558061753; hg19: chr8-145739101;