rs368335924

chr8-144516627-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004260.4(RECQL4):c.492G>A(p.Glu164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,610,404 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (16 hom., cov: 34)
  • Exomes 𝑓: 0.0041 (246 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.340

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=-0.84).
• BP6: Variant 8-144516627-C-T is Benign according to our data. Variant chr8-144516627-C-T is described in ClinVar as [Benign]. Clinvar id is 239777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144516627-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4	c.492G>A	p.Glu164=	synonymous_variant	5/21	ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6	c.492G>A	p.Glu164=	synonymous_variant	5/21	1	NM_004260.4	P1
RECQL4	ENST00000621189.4	c.-580G>A		5_prime_UTR_variant	4/20	1
RECQL4	ENST00000524998.1	c.228-214G>A		intron_variant		3
RECQL4	ENST00000534538.1	c.*296G>A		3_prime_UTR_variant, NMD_transcript_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 352 AN: 152158 Hom.: 16 Cov.: 34

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00846 AC: 2061 AN: 243568 Hom.: 81 AF XY: 0.0113 AC XY: 1504 AN XY: 133060

Gnomad AFR exome AF: 0.0000671

Gnomad AMR exome AF: 0.000441

Gnomad ASJ exome AF: 0.00368

Gnomad EAS exome AF: 0.000113

Gnomad SAS exome AF: 0.0654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000729

Gnomad OTH exome AF: 0.00270

GnomAD4 exome AF: 0.00413 AC: 6023 AN: 1458128 Hom.: 246 Cov.: 35 AF XY: 0.00600 AC XY: 4354 AN XY: 725278

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.000383

Gnomad4 ASJ exome AF: 0.00400

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0647

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000513

Gnomad4 OTH exome AF: 0.00425

GnomAD4 genome AF: 0.00232 AC: 353 AN: 152276 Hom.: 16 Cov.: 34 AF XY: 0.00359 AC XY: 267 AN XY: 74448

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0685

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000521 Hom.: 1

Bravo AF: 0.000525

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 19, 2020

- -

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 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.2
Dann	Benign	0.62

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: rs368335924; hg19: chr8-145742011;