rs34496005

chr8-144517104-G-A

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.300C>T(p.Gly100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,612,392 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (31 hom., cov: 34)
  • Exomes 𝑓: 0.0011 (28 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.06

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-144517104-G-A is Benign according to our data. Variant chr8-144517104-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1631/152376) while in subpopulation AFR AF= 0.0371 (1542/41586). AF 95% confidence interval is 0.0355. There are 31 homozygotes in gnomad4. There are 754 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4	c.300C>T	p.Gly100=	synonymous_variant	4/21	ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6	c.300C>T	p.Gly100=	synonymous_variant	4/21	1	NM_004260.4	P1

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1625 AN: 152258 Hom.: 31 Cov.: 34

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00259 AC: 638 AN: 246522 Hom.: 14 AF XY: 0.00200 AC XY: 269 AN XY: 134616

Gnomad AFR exome AF: 0.0351

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.000223

Gnomad SAS exome AF: 0.00134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000135

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00115 AC: 1674 AN: 1460016 Hom.: 28 Cov.: 31 AF XY: 0.00100 AC XY: 727 AN XY: 726288

Gnomad4 AFR exome AF: 0.0384

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00106

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000747

Gnomad4 OTH exome AF: 0.00254

GnomAD4 genome AF: 0.0107 AC: 1631 AN: 152376 Hom.: 31 Cov.: 34 AF XY: 0.0101 AC XY: 754 AN XY: 74516

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00529 Hom.: 8

Bravo AF: 0.0119

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

RECQL4-related condition Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 18, 2019

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

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 03, 2021

- -

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.40
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs34496005; hg19: chr8-145742488; COSMIC: COSV104618536; COSMIC: COSV104618536;