rs34735741

chr8-144513266-G-Achr8-144513266-G-Cchr8-144513266-G-T

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.2415C>T(p.Ala805=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,593,724 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A805A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0056 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (17 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -5.73

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 8-144513266-G-A is Benign according to our data. Variant chr8-144513266-G-A is described in ClinVar as [Benign]. Clinvar id is 239725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.73 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00556 (845/152080) while in subpopulation AFR AF= 0.019 (787/41392). AF 95% confidence interval is 0.0179. There are 7 homozygotes in gnomad4. There are 406 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4	c.2415C>T	p.Ala805=	synonymous_variant	14/21	ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6	c.2415C>T	p.Ala805=	synonymous_variant	14/21	1	NM_004260.4	P1
RECQL4	ENST00000621189.4	c.1344C>T	p.Ala448=	synonymous_variant	13/20	1
	ENST00000580385.1	n.272-340G>A		intron_variant, non_coding_transcript_variant		3
RECQL4	ENST00000534626.6	c.635-128C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00549 AC: 835 AN: 151962 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00149 AC: 327 AN: 219740 Hom.: 5 AF XY: 0.00123 AC XY: 151 AN XY: 122438

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.00157

Gnomad ASJ exome AF: 0.000530

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000242

Gnomad OTH exome AF: 0.00126

GnomAD4 exome AF: 0.000685 AC: 987 AN: 1441644 Hom.: 17 Cov.: 48 AF XY: 0.000607 AC XY: 435 AN XY: 716902

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.00158

Gnomad4 ASJ exome AF: 0.00100

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000187

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00556 AC: 845 AN: 152080 Hom.: 7 Cov.: 33 AF XY: 0.00546 AC XY: 406 AN XY: 74352

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00171 Hom.: 2

Bravo AF: 0.00623

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 28, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 03, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 01, 2019

- -

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

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	1.5
Dann	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs34735741; hg19: chr8-145738649;