chr8-144511449-G-A

Variant names:

• chr8-144511449-G-A
• rs201384843
• NM_004260.4:c.3609C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004260.4(RECQL4):​c.3609C>T​(p.Leu1203Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,612,508 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L1203L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0034 (7 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0580
• Publications: 7 publications found

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]

SLC33A2 (HGNC:25157): (major facilitator superfamily domain containing 3) Predicted to enable solute:proton symporter activity. Predicted to be involved in proton transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 8-144511449-G-A is Benign according to our data. Variant chr8-144511449-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 239770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.058 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.3609C>T	p.Leu1203Leu	synonymous	Exon 21 of 21	NP_004251.4
	RECQL4	NM_001413019.1		c.3684C>T	p.Leu1228Leu	synonymous	Exon 20 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.3618C>T	p.Leu1206Leu	synonymous	Exon 21 of 21	NP_001399965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.3609C>T	p.Leu1203Leu	synonymous	Exon 21 of 21	ENSP00000482313.2
	RECQL4	ENST00000621189.4	TSL:1	c.2538C>T	p.Leu846Leu	synonymous	Exon 20 of 20	ENSP00000483145.1
	RECQL4	ENST00000531875.2	TSL:5	c.864C>T	p.Leu288Leu	synonymous	Exon 6 of 6	ENSP00000477910.1

Frequencies

GnomAD3 genomes AF: 0.00277 AC: 421 AN: 152234 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00463

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00256 AC: 635 AN: 247896 AF XY: 0.00273

Gnomad AFR exome AF: 0.000391

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00390

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00172

Gnomad NFE exome AF: 0.00419

Gnomad OTH exome AF: 0.00382

GnomAD4 exome AF: 0.00342 AC: 4998 AN: 1460156 Hom.: 7 Cov.: 32 AF XY: 0.00352 AC XY: 2553 AN XY: 726314

African (AFR) AF: 0.000448 AC: 15 AN: 33478

American (AMR) AF: 0.00154 AC: 69 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00344 AC: 90 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86258

European-Finnish (FIN) AF: 0.00198 AC: 103 AN: 52070

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5766

European-Non Finnish (NFE) AF: 0.00405 AC: 4505 AN: 1111694

Other (OTH) AF: 0.00263 AC: 159 AN: 60346

GnomAD4 genome AF: 0.00276 AC: 421 AN: 152352 Hom.: 1 Cov.: 34 AF XY: 0.00250 AC XY: 186 AN XY: 74498

African (AFR) AF: 0.000649 AC: 27 AN: 41584

American (AMR) AF: 0.00274 AC: 42 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00463 AC: 315 AN: 68032

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00379 Hom.: 2

Bravo AF: 0.00270

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00502

EpiControl AF: 0.00474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Dec 21, 2017

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dec 13, 2022

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RECQL4: BP4, BP7

Mar 16, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27247962)

Hereditary cancer-predisposing syndrome Benign:1

May 28, 2021

Sema4, Sema4

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

Baller-Gerold syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.52
DANN	Benign	0.84
PhyloP100		0.058
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201384843; hg19: chr8-145736832; COSMIC: COSV56741306; COSMIC: COSV56741306;